Pro-resolving Mediators

  • William Antonio Gonçalves
  • Alesandra Côrte Reis Melão
  • Mauro Martins Teixeira
  • Barbara Maximino RezendeEmail author
  • Vanessa PinhoEmail author


Acute inflammation is a self-limiting process of the immune system, which resolves through the initiation of a program referred to as the resolution of inflammation. It has been argued that uncontrolled inflammation may be the basis of a variety of chronic inflammatory and autoimmune diseases. The resolution of inflammation is an active process coordinated by the production of proresolving mediators. The release of proresolving mediators prevents further migration of granulocytes, and increases leukocyte apoptosis. Moreover, some proresolving molecules are able to promote the infiltration of nonphlogistic macrophages, which are fundamental cells to efferocyte of apoptotic granulocytes. This event, in turn, triggers macrophage reprogramming towards more restorative and resolutive roles, thereby promoting resolution and reestablishment of tissue homeostasis. Here, we summarize the most prominent pro-resolving mediators relevant to the resolution of inflammation.


Inflammation Pro-resolving mediators Resolution 


  1. 1.
    Alessandri AL, Sousa LP, Lucas CD, Rossi AG, Pinho V, Teixeira MM (2013) Resolution of inflammation: mechanisms and opportunity for drug development. Pharmacol Ther 139(2):189–212. CrossRefPubMedGoogle Scholar
  2. 2.
    Sugimoto MA, Sousa LP, Pinho V, Perretti M, Teixeira MM (2016) Resolution of inflammation: what controls its onset? Front Immunol 7:160. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Chiang N, Serhan CN (2017) Structural elucidation and physiologic functions of specialized pro-resolving mediators and their receptors. Mol Asp Texto Med.
  4. 4.
    Chiang N, de la Rosa X, Libreros S, Serhan CN (2017) Novel resolvin D2 receptor axis in infectious inflammation. J Immunol 198(2):842–851. CrossRefPubMedGoogle Scholar
  5. 5.
    Buckley CD, Gilroy DW, Serhan CN, Stockinger B, Tak PP (2013) The resolution of inflammation. Nat Rev Immunol 13(1):59–66. CrossRefPubMedGoogle Scholar
  6. 6.
    Mirakaj V, Dalli J, Granja T, Rosenberger P, Serhan CN (2014) Vagus nerve controls resolution and pro-resolving mediators of inflammation. J Exp Med 211(6):1037–1048. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Schwab JM, Chiang N, Arita M, Serhan CN (2007) Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 447(7146):869–874. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Fullerton JN, Gilroy DW (2016) Resolution of inflammation: a new therapeutic frontier. Nat Rev Drug Discov 15(8):551–567. CrossRefPubMedGoogle Scholar
  9. 9.
    Perretti CT, Munch SB (2015) On estimating the reliability of ecological forecasts. J Theor Biol 372:211–216. CrossRefPubMedGoogle Scholar
  10. 10.
    Perretti M (2015) The resolution of inflammation: new mechanisms in patho-physiology open opportunities for pharmacology. Semin Immunol 27(3):145–148. CrossRefPubMedGoogle Scholar
  11. 11.
    Schwab R, Schumacher O, Junge K, Binnebosel M, Klinge U, Schumpelick V (2007) Fibrin sealant for mesh fixation in Lichtenstein repair: biomechanical analysis of different techniques. Hernia 11(2):139–145. CrossRefPubMedGoogle Scholar
  12. 12.
    Ortega-Gomez A, Perretti M, Soehnlein O (2013) Resolution of inflammation: an integrated view. EMBO Mol Med 5(5):661–674. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Sousa LP, Carmo AF, Rezende BM, Lopes F, Silva DM, Alessandri AL, Bonjardim CA, Rossi AG, Teixeira MM, Pinho V (2009) Cyclic AMP enhances resolution of allergic pleurisy by promoting inflammatory cell apoptosis via inhibition of PI3K/Akt and NF-kappaB. Biochem Pharmacol 78(4):396–405. CrossRefPubMedGoogle Scholar
  14. 14.
    Sousa LP, Lopes F, Silva DM, Tavares LP, Vieira AT, Rezende BM, Carmo AF, Russo RC, Garcia CC, Bonjardim CA, Alessandri AL, Rossi AG, Pinho V, Teixeira MM (2010) PDE4 inhibition drives resolution of neutrophilic inflammation by inducing apoptosis in a PKA-PI3K/Akt-dependent and NF-kappaB-independent manner. J Leukoc Biol 87(5):895–904. CrossRefPubMedGoogle Scholar
  15. 15.
    Perretti M, Cooper D, Dalli J, Norling LV (2017) Immune resolution mechanisms in inflammatory arthritis. Nat Rev Rheumatol 13(2):87–99. CrossRefPubMedGoogle Scholar
  16. 16.
    Tabas I, Glass CK (2013) Anti-inflammatory therapy in chronic disease: challenges and opportunities. Science 339(6116):166–172. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Perez DA, Vago JP, Athayde RM, Reis AC, Teixeira MM, Sousa LP, Pinho V (2014) Switching off key signaling survival molecules to switch on the resolution of inflammation. Mediat Inflamm 2014:829851. CrossRefGoogle Scholar
  18. 18.
    Wallace JL, Blackler RW, Chan MV, Da Silva GJ, Elsheikh W, Flannigan KL, Gamaniek I, Manko A, Wang L, Motta JP, Buret AG (2015) Anti-inflammatory and cytoprotective actions of hydrogen sulfide: translation to therapeutics. Antioxid Redox Signal 22(5):398–410. CrossRefPubMedGoogle Scholar
  19. 19.
    Serhan CN, Krishnamoorthy S, Recchiuti A, Chiang N (2011) Novel anti-inflammatory--pro-resolving mediators and their receptors. Curr Top Med Chem 11(6):629–647CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Samuelsson B (1987) An elucidation of the arachidonic acid cascade. Discovery of prostaglandins, thromboxane and leukotrienes. Drugs 33(Suppl 1):2–9CrossRefPubMedGoogle Scholar
  21. 21.
    Serhan CN, Chiang N (2008) Endogenous pro-resolving and anti-inflammatory lipid mediators: a new pharmacologic genus. Br J Pharmacol 153(Suppl 1):S200–S215. CrossRefPubMedGoogle Scholar
  22. 22.
    Buckley CD, Gilroy DW, Serhan CN (2014) Proresolving lipid mediators and mechanisms in the resolution of acute inflammation. Immunity 40(3):315–327. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Buckley CD, Halder S, Hardie D, Reynolds G, Torensma R, De Villeroche VJ, Brouty-Boye D, Isacke CM (2005) Report on antibodies submitted to the stromal cell section of HLDA8. Cell Immunol 236(1–2):29–41. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Serhan CN, Lundberg U, Weissmann G, Samuelsson B (1984) Formation of leukotrienes and hydroxy acids by human neutrophils and platelets exposed to monosodium urate. Prostaglandins 27(4):563–581CrossRefPubMedGoogle Scholar
  25. 25.
    Serhan CN (1994) Lipoxin biosynthesis and its impact in inflammatory and vascular events. Biochim Biophys Acta 1212(1):1–25CrossRefPubMedGoogle Scholar
  26. 26.
    Serhan CN (2017) Discovery of specialized pro-resolving mediators marks the dawn of resolution physiology and pharmacology. Mol Asp Med.
  27. 27.
    Tagoe CE, Marjanovic N, Park JY, Chan ES, Abeles AM, Attur M, Abramson SB, Pillinger MH (2008) Annexin-1 mediates TNF-alpha-stimulated matrix metalloproteinase secretion from rheumatoid arthritis synovial fibroblasts. J Immunol 181(4):2813–2820CrossRefPubMedGoogle Scholar
  28. 28.
    Serhan CN, Hamberg M, Samuelsson B (1984) Lipoxins: novel series of biologically active compounds formed from arachidonic acid in human leukocytes. Proc Natl Acad Sci U S A 81(17):5335–5339CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Levy BD, Bertram S, Tai HH, Israel E, Fischer A, Drazen JM, Serhan CN (1993) Agonist-induced lipoxin A4 generation: detection by a novel lipoxin A4-ELISA. Lipids 28(12):1047–1053CrossRefPubMedGoogle Scholar
  30. 30.
    Basil MC, Levy BD (2016) Specialized pro-resolving mediators: endogenous regulators of infection and inflammation. Nat Rev Immunol 16(1):51–67. CrossRefPubMedGoogle Scholar
  31. 31.
    Ryan A, Godson C (2010) Lipoxins: regulators of resolution. Curr Opin Pharmacol 10(2):166–172. CrossRefPubMedGoogle Scholar
  32. 32.
    Lindgren JA, Edenius C (1993) Transcellular biosynthesis of leukotrienes and lipoxins via leukotriene A4 transfer. Trends Pharmacol Sci 14(10):351–354CrossRefPubMedGoogle Scholar
  33. 33.
    Fiore S, Serhan CN (1990) Formation of lipoxins and leukotrienes during receptor-mediated interactions of human platelets and recombinant human granulocyte/macrophage colony-stimulating factor-primed neutrophils. J Exp Med 172(5):1451–1457CrossRefPubMedGoogle Scholar
  34. 34.
    Serhan CN, Sheppard KA (1990) Lipoxin formation during human neutrophil-platelet interactions. Evidence for the transformation of leukotriene A4 by platelet 12-lipoxygenase in vitro. J Clin Invest 85(3):772–780. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Claria J, Serhan CN (1995) Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. Proc Natl Acad Sci U S A 92(21):9475–9479CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Chiang N, Takano T, Clish CB, Petasis NA, Tai HH, Serhan CN (1998) Aspirin-triggered 15-epi-lipoxin A4 (ATL) generation by human leukocytes and murine peritonitis exudates: development of a specific 15-epi-LXA4 ELISA. J Pharmacol Exp Ther 287(2):779–790PubMedGoogle Scholar
  37. 37.
    Claria J, Lee MH, Serhan CN (1996) Aspirin-triggered lipoxins (15-epi-LX) are generated by the human lung adenocarcinoma cell line (A549)-neutrophil interactions and are potent inhibitors of cell proliferation. Mol Med 2(5):583–596PubMedCrossRefGoogle Scholar
  38. 38.
    Chiang N, Serhan CN, Dahlen SE, Drazen JM, Hay DW, Rovati GE, Shimizu T, Yokomizo T, Brink C (2006) The lipoxin receptor ALX: potent ligand-specific and stereoselective actions in vivo. Pharmacol Rev 58(3):463–487. CrossRefPubMedGoogle Scholar
  39. 39.
    Corminboeuf O, Leroy X (2015) FPR2/ALXR agonists and the resolution of inflammation. J Med Chem 58(2):537–559. CrossRefPubMedGoogle Scholar
  40. 40.
    Cattaneo F, Parisi M, Ammendola R (2013) Distinct signaling cascades elicited by different formyl peptide receptor 2 (FPR2) agonists. Int J Mol Sci 14(4):7193–7230. CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Maderna P, Godson C (2009) Lipoxins: resolutionary road. Br J Pharmacol 158(4):947–959. CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Barnig C, Cernadas M, Dutile S, Liu X, Perrella MA, Kazani S, Wechsler ME, Israel E, Levy BD (2013) Lipoxin A4 regulates natural killer cell and type 2 innate lymphoid cell activation in asthma. Sci Transl Med 5(174):174ra126. CrossRefGoogle Scholar
  43. 43.
    Ye RD, Boulay F, Wang JM, Dahlgren C, Gerard C, Parmentier M, Serhan CN, Murphy PM (2009) International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the formyl peptide receptor (FPR) family. Pharmacol Rev 61(2):119–161. CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Bonnans C, Fukunaga K, Levy MA, Levy BD (2006) Lipoxin A(4) regulates bronchial epithelial cell responses to acid injury. Am J Pathol 168(4):1064–1072. CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Maddox JF, Hachicha M, Takano T, Petasis NA, Fokin VV, Serhan CN (1997) Lipoxin A4 stable analogs are potent mimetics that stimulate human monocytes and THP-1 cells via a G-protein-linked lipoxin A4 receptor. J Biol Chem 272(11):6972–6978CrossRefPubMedGoogle Scholar
  46. 46.
    Fiore S, Maddox JF, Perez HD, Serhan CN (1994) Identification of a human cDNA encoding a functional high affinity lipoxin A4 receptor. J Exp Med 180(1):253–260CrossRefPubMedGoogle Scholar
  47. 47.
    Sodin-Semrl S, Taddeo B, Tseng D, Varga J, Fiore S (2000) Lipoxin A4 inhibits IL-1 beta-induced IL-6, IL-8, and matrix metalloproteinase-3 production in human synovial fibroblasts and enhances synthesis of tissue inhibitors of metalloproteinases. J Immunol 164(5):2660–2666CrossRefPubMedGoogle Scholar
  48. 48.
    Souza DG, Fagundes CT, Amaral FA, Cisalpino D, Sousa LP, Vieira AT, Pinho V, Nicoli JR, Vieira LQ, Fierro IM, Teixeira MM (2007) The required role of endogenously produced lipoxin A4 and annexin-1 for the production of IL-10 and inflammatory hyporesponsiveness in mice. J Immunol 179(12):8533–8543CrossRefPubMedGoogle Scholar
  49. 49.
    Calder PC (2013) Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? Br J Clin Pharmacol 75(3):645–662. CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Qu Q, Xuan W, Fan GH (2015) Roles of resolvins in the resolution of acute inflammation. Cell Biol Int 39(1):3–22. CrossRefPubMedGoogle Scholar
  51. 51.
    Serhan CN, Petasis NA (2011) Resolvins and protectins in inflammation resolution. Chem Rev 111(10):5922–5943. CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G, Moussignac RL (2002) Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med 196(8):1025–1037CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Serhan CN, Clish CB, Brannon J, Colgan SP, Chiang N, Gronert K (2000) Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. J Exp Med 192(8):1197–1204CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Arita M, Ohira T, Sun YP, Elangovan S, Chiang N, Serhan CN (2007) Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. J Immunol 178(6):3912–3917CrossRefPubMedGoogle Scholar
  55. 55.
    Yamada T, Tani Y, Nakanishi H, Taguchi R, Arita M, Arai H (2011) Eosinophils promote resolution of acute peritonitis by producing proresolving mediators in mice. FASEB J 25(2):561–568. CrossRefPubMedGoogle Scholar
  56. 56.
    Isobe Y, Arita M, Matsueda S, Iwamoto R, Fujihara T, Nakanishi H, Taguchi R, Masuda K, Sasaki K, Urabe D, Inoue M, Arai H (2012) Identification and structure determination of novel anti-inflammatory mediator resolvin E3, 17,18-dihydroxyeicosapentaenoic acid. J Biol Chem 287(13):10525–10534. CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Serhan CN (2017) Treating inflammation and infection in the 21st century: new hints from decoding resolution mediators and mechanisms. FASEB J 31(4):1273–1288. CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Arita M, Bianchini F, Aliberti J, Sher A, Chiang N, Hong S, Yang R, Petasis NA, Serhan CN (2005) Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J Exp Med 201(5):713–722. CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Werz O, Szellas D, Steinhilber D, Radmark O (2002) Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPK-activated protein kinase 2 (MK2). J Biol Chem 277(17):14793–14800. CrossRefPubMedGoogle Scholar
  60. 60.
    Ji RR, Xu ZZ, Strichartz G, Serhan CN (2011) Emerging roles of resolvins in the resolution of inflammation and pain. Trends Neurosci 34(11):599–609. CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Fukunaga K, Kohli P, Bonnans C, Fredenburgh LE, Levy BD (2005) Cyclooxygenase 2 plays a pivotal role in the resolution of acute lung injury. J Immunol 174(8):5033–5039CrossRefPubMedGoogle Scholar
  62. 62.
    Stables MJ, Gilroy DW (2011) Old and new generation lipid mediators in acute inflammation and resolution. Prog Lipid Res 50(1):35–51. CrossRefPubMedGoogle Scholar
  63. 63.
    Oh SF, Pillai PS, Recchiuti A, Yang R, Serhan CN (2011) Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammation. J Clin Invest 121(2):569–581. CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Arita M, Yoshida M, Hong S, Tjonahen E, Glickman JN, Petasis NA, Blumberg RS, Serhan CN (2005) Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Proc Natl Acad Sci U S A 102(21):7671–7676. CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Wittamer V, Franssen JD, Vulcano M, Mirjolet JF, Le Poul E, Migeotte I, Brezillon S, Tyldesley R, Blanpain C, Detheux M, Mantovani A, Sozzani S, Vassart G, Parmentier M, Communi D (2003) Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids. J Exp Med 198(7):977–985. CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Campbell EL, MacManus CF, Kominsky DJ, Keely S, Glover LE, Bowers BE, Scully M, Bruyninckx WJ, Colgan SP (2010) Resolvin E1-induced intestinal alkaline phosphatase promotes resolution of inflammation through LPS detoxification. Proc Natl Acad Sci U S A 107(32):14298–14303. CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Ishida T, Yoshida M, Arita M, Nishitani Y, Nishiumi S, Masuda A, Mizuno S, Takagawa T, Morita Y, Kutsumi H, Inokuchi H, Serhan CN, Blumberg RS, Azuma T (2010) Resolvin E1, an endogenous lipid mediator derived from eicosapentaenoic acid, prevents dextran sulfate sodium-induced colitis. Inflamm Bowel Dis 16(1):87–95. CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Haworth O, Cernadas M, Levy BD (2011) NK cells are effectors for resolvin E1 in the timely resolution of allergic airway inflammation. J Immunol 186(11):6129–6135. CrossRefPubMedGoogle Scholar
  69. 69.
    Ohira T, Arita M, Omori K, Recchiuti A, Van Dyke TE, Serhan CN (2010) Resolvin E1 receptor activation signals phosphorylation and phagocytosis. J Biol Chem 285(5):3451–3461. CrossRefPubMedGoogle Scholar
  70. 70.
    Yokomizo T, Izumi T, Chang K, Takuwa Y, Shimizu T (1997) A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis. Nature 387(6633):620–624. CrossRefPubMedGoogle Scholar
  71. 71.
    Freire MO, Dalli J, Serhan CN, Van Dyke TE (2017) Neutrophil resolvin E1 receptor expression and function in type 2 diabetes. J Immunol 198(2):718–728. CrossRefPubMedGoogle Scholar
  72. 72.
    Serhan CN, Chiang N, Dalli J (2017) New pro-resolving n-3 mediators bridge resolution of infectious inflammation to tissue regeneration. Mol Asp Med.
  73. 73.
    Kohli P, Levy BD (2009) Resolvins and protectins: mediating solutions to inflammation. Br J Pharmacol 158(4):960–971. CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Marcheselli VL, Mukherjee PK, Arita M, Hong S, Antony R, Sheets K, Winkler JW, Petasis NA, Serhan CN, Bazan NG (2010) Neuroprotectin D1/protectin D1 stereoselective and specific binding with human retinal pigment epithelial cells and neutrophils. Prostaglandins Leukot Essent Fatty Acids 82(1):27–34. CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Serhan CN, Gotlinger K, Hong S, Arita M (2004) Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their aspirin-triggered endogenous epimers: an overview of their protective roles in catabasis. Prostaglandins Other Lipid Mediat 73(3–4):155–172CrossRefPubMedGoogle Scholar
  76. 76.
    Marcheselli VL, Hong S, Lukiw WJ, Tian XH, Gronert K, Musto A, Hardy M, Gimenez JM, Chiang N, Serhan CN, Bazan NG (2003) Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 278(44):43807–43817. CrossRefPubMedGoogle Scholar
  77. 77.
    Norling LV, Headland SE, Dalli J, Arnardottir HH, Haworth O, Jones HR, Irimia D, Serhan CN, Perretti M (2016) Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis. JCI Insight 1(5):e85922. CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Giera M, Ioan-Facsinay A, Toes R, Gao F, Dalli J, Deelder AM, Serhan CN, Mayboroda OA (2012) Lipid and lipid mediator profiling of human synovial fluid in rheumatoid arthritis patients by means of LC-MS/MS. Biochim Biophys Acta 1821(11):1415–1424. CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Chatterjee A, Komshian S, Sansbury BE, Wu B, Mottola G, Chen M, Spite M, Conte MS (2017) Biosynthesis of proresolving lipid mediators by vascular cells and tissues. FASEB J 31(8):3393–3402. CrossRefPubMedGoogle Scholar
  80. 80.
    Krishnamoorthy S, Recchiuti A, Chiang N, Yacoubian S, Lee CH, Yang R, Petasis NA, Serhan CN (2010) Resolvin D1 binds human phagocytes with evidence for proresolving receptors. Proc Natl Acad Sci U S A 107(4):1660–1665. CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Bennett M, Gilroy DW (2016) Lipid mediators in inflammation. Microbiol Spectr 4(6).
  82. 82.
    Recchiuti A, Krishnamoorthy S, Fredman G, Chiang N, Serhan CN (2011) MicroRNAs in resolution of acute inflammation: identification of novel resolvin D1-miRNA circuits. FASEB J 25(2):544–560. CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Dalli J, Colas RA, Serhan CN (2013) Novel n-3 immunoresolvents: structures and actions. Sci Rep 3:1940. CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Chiang N, Fredman G, Backhed F, Oh SF, Vickery T, Schmidt BA, Serhan CN (2012) Infection regulates pro-resolving mediators that lower antibiotic requirements. Nature 484(7395):524–528. CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Chiang N, Dalli J, Colas RA, Serhan CN (2015) Identification of resolvin D2 receptor mediating resolution of infections and organ protection. J Exp Med 212(8):1203–1217. CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Zhang MJ, Sansbury BE, Hellmann J, Baker JF, Guo L, Parmer CM, Prenner JC, Conklin DJ, Bhatnagar A, Creager MA, Spite M (2016) Resolvin D2 enhances postischemic revascularization while resolving inflammation. Circulation 134(9):666–680. CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Pascoal LB, Bombassaro B, Ramalho AF, Coope A, Moura RF, Correa-da-Silva F, Ignacio-Souza L, Razolli D, de Oliveira D, Catharino R, Velloso LA (2017) Resolvin RvD2 reduces hypothalamic inflammation and rescues mice from diet-induced obesity. J Neuroinflammation 14(1):5. CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Serhan CN, Gotlinger K, Hong S, Lu Y, Siegelman J, Baer T, Yang R, Colgan SP, Petasis NA (2006) Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes. J Immunol 176(3):1848–1859CrossRefPubMedGoogle Scholar
  89. 89.
    Mukherjee PK, Marcheselli VL, Serhan CN, Bazan NG (2004) Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc Natl Acad Sci U S A 101(22):8491–8496. CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG (2005) A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J Clin Invest 115(10):2774–2783. CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Schwab S, Kuefner MA (2007) Ureterolithiasis with right urine blockage. Dtsch Med Wochenschr 132(31–32):1627–1628. CrossRefPubMedGoogle Scholar
  92. 92.
    Dalli J, Consalvo AP, Ray V, Di Filippo C, D’Amico M, Mehta N, Perretti M (2013) Proresolving and tissue-protective actions of annexin A1-based cleavage-resistant peptides are mediated by formyl peptide receptor 2/lipoxin A4 receptor. J Immunol 190(12):6478–6487. CrossRefPubMedGoogle Scholar
  93. 93.
    Serhan CN, Arita M, Hong S, Gotlinger K (2004) Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their endogenous aspirin-triggered epimers. Lipids 39(11):1125–1132CrossRefPubMedGoogle Scholar
  94. 94.
    Hong JH (2003) Synthesis and antiviral evaluation of novel 3′- and 4′-doubly branched carbocyclic nucleosides as potential antiviral agents. Arch Pharm Res 26(12):1109–1116CrossRefPubMedGoogle Scholar
  95. 95.
    Levy BD, Kohli P, Gotlinger K, Haworth O, Hong S, Kazani S, Israel E, Haley KJ, Serhan CN (2007) Protectin D1 is generated in asthma and dampens airway inflammation and hyperresponsiveness. J Immunol 178(1):496–502CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Jones ML, Mark PJ, Keelan JA, Barden A, Mas E, Mori TA, Waddell BJ (2013) Maternal dietary omega-3 fatty acid intake increases resolvin and protectin levels in the rat placenta. J Lipid Res 54(8):2247–2254. CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Hong S, Gronert K, Devchand PR, Moussignac RL, Serhan CN (2003) Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti-inflammation. J Biol Chem 278(17):14677–14687. CrossRefPubMedGoogle Scholar
  98. 98.
    Ariel A, Li PL, Wang W, Tang WX, Fredman G, Hong S, Gotlinger KH, Serhan CN (2005) The docosatriene protectin D1 is produced by TH2 skewing and promotes human T cell apoptosis via lipid raft clustering. J Biol Chem 280(52):43079–43086. CrossRefPubMedGoogle Scholar
  99. 99.
    Kalinec GM, Lomberk G, Urrutia RA, Kalinec F (2017) Resolution of cochlear inflammation: novel target for preventing or ameliorating drug-, noise- and age-related hearing loss. Front Cell Neurosci 11:192. CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Serhan CN, Dalli J, Karamnov S, Choi A, Park CK, Xu ZZ, Ji RR, Zhu M, Petasis NA (2012) Macrophage proresolving mediator maresin 1 stimulates tissue regeneration and controls pain. FASEB J 26(4):1755–1765. CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Deng B, Wang CW, Arnardottir HH, Li Y, Cheng CY, Dalli J, Serhan CN (2014) Maresin biosynthesis and identification of maresin 2, a new anti-inflammatory and pro-resolving mediator from human macrophages. PLoS One 9(7):e102362. CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Abdulnour RE, Dalli J, Colby JK, Krishnamoorthy N, Timmons JY, Tan SH, Colas RA, Petasis NA, Serhan CN, Levy BD (2014) Maresin 1 biosynthesis during platelet-neutrophil interactions is organ-protective. Proc Natl Acad Sci U S A 111(46):16526–16531. CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Hong S, Tian H, Lu Y, Laborde JM, Muhale FA, Wang Q, Alapure BV, Serhan CN, Bazan NG (2014) Neuroprotectin/protectin D1: endogenous biosynthesis and actions on diabetic macrophages in promoting wound healing and innervation impaired by diabetes. Am J Physiol Cell Physiol 307(11):C1058–C1067. CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Poorani R, Bhatt AN, Dwarakanath BS, Das UN (2016) COX-2, aspirin and metabolism of arachidonic, eicosapentaenoic and docosahexaenoic acids and their physiological and clinical significance. Eur J Pharmacol 785:116–132. CrossRefPubMedGoogle Scholar
  105. 105.
    Parente L, Solito E (2004) Annexin 1: more than an anti-phospholipase protein. Inflammation research: official journal of the European Histamine Research Society [et al] 53(4):125–132. CrossRefGoogle Scholar
  106. 106.
    Dreier R, Schmid KW, Gerke V, Riehemann K (1998) Differential expression of annexins I, II and IV in human tissues: an immunohistochemical study. Histochem Cell Biol 110(2):137–148CrossRefPubMedGoogle Scholar
  107. 107.
    Babbin BA, Laukoetter MG, Nava P, Koch S, Lee WY, Capaldo CT, Peatman E, Severson EA, Flower RJ, Perretti M, Parkos CA, Nusrat A (2008) Annexin A1 regulates intestinal mucosal injury, inflammation, and repair. J Immunol 181(7):5035–5044CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Hullin F, Raynal P, Ragab-Thomas JM, Fauvel J, Chap H (1989) Effect of dexamethasone on prostaglandin synthesis and on lipocortin status in human endothelial cells. Inhibition of prostaglandin I2 synthesis occurring without alteration of arachidonic acid liberation and of lipocortin synthesis. J Biol Chem 264(6):3506–3513PubMedGoogle Scholar
  109. 109.
    Sampey AV, Hutchinson P, Morand EF (2000) Annexin I and dexamethasone effects on phospholipase and cyclooxygenase activity in human synoviocytes. Mediat Inflamm 9(3–4):125–132. CrossRefGoogle Scholar
  110. 110.
    Jia Y, Morand EF, Song W, Cheng Q, Stewart A, Yang YH (2013) Regulation of lung fibroblast activation by annexin A1. J Cell Physiol 228(2):476–484. CrossRefPubMedGoogle Scholar
  111. 111.
    Neymeyer H, Labes R, Reverte V, Saez F, Stroh T, Dathe C, Hohberger S, Zeisberg M, Muller GA, Salazar J, Bachmann S, Paliege A (2015) Activation of annexin A1 signalling in renal fibroblasts exerts antifibrotic effects. Acta Physiol (Oxf) 215(3):144–158. CrossRefGoogle Scholar
  112. 112.
    Bizzarro V, Fontanella B, Franceschelli S, Pirozzi M, Christian H, Parente L, Petrella A (2010) Role of Annexin A1 in mouse myoblast cell differentiation. J Cell Physiol 224(3):757–765. CrossRefPubMedGoogle Scholar
  113. 113.
    D’Acquisto F, Merghani A, Lecona E, Rosignoli G, Raza K, Buckley CD, Flower RJ, Perretti M (2007) Annexin-1 modulates T-cell activation and differentiation. Blood 109(3):1095–1102. CrossRefPubMedGoogle Scholar
  114. 114.
    Perretti M, D'Acquisto F (2009) Annexin A1 and glucocorticoids as effectors of the resolution of inflammation. Nat Rev Immunol 9(1):62–70. CrossRefPubMedPubMedCentralGoogle Scholar
  115. 115.
    Christmas P, Callaway J, Fallon J, Jones J, Haigler HT (1991) Selective secretion of annexin 1, a protein without a signal sequence, by the human prostate gland. J Biol Chem 266(4):2499–2507PubMedGoogle Scholar
  116. 116.
    Cooray SN, Gobbetti T, Montero-Melendez T, McArthur S, Thompson D, Clark AJ, Flower RJ, Perretti M (2013) Ligand-specific conformational change of the G-protein-coupled receptor ALX/FPR2 determines proresolving functional responses. Proc Natl Acad Sci U S A 110(45):18232–18237. CrossRefPubMedPubMedCentralGoogle Scholar
  117. 117.
    Solito E, Kamal A, Russo-Marie F, Buckingham JC, Marullo S, Perretti M (2003) A novel calcium-dependent proapoptotic effect of annexin 1 on human neutrophils. FASEB J 17(11):1544–1546. CrossRefPubMedGoogle Scholar
  118. 118.
    Sawmynaden P, Perretti M (2006) Glucocorticoid upregulation of the annexin-A1 receptor in leukocytes. Biochem Biophys Res Commun 349(4):1351–1355. CrossRefPubMedGoogle Scholar
  119. 119.
    Catania A (2007) The melanocortin system in leukocyte biology. J Leukoc Biol 81(2):383–392. CrossRefPubMedGoogle Scholar
  120. 120.
    Loram LC, Culp ME, Connolly-Strong EC, Sturgill-Koszycki S (2015) Melanocortin peptides: potential targets in systemic lupus erythematosus. Inflammation 38(1):260–271. CrossRefPubMedGoogle Scholar
  121. 121.
    Yang Y, Harmon CM (2017) Molecular signatures of human melanocortin receptors for ligand binding and signaling. Biochim Biophys Acta 1863(10 Pt A):2436–2447. CrossRefPubMedGoogle Scholar
  122. 122.
    Gantz I, Fong TM (2003) The melanocortin system. Am J Physiol Endocrinol Metab 284(3):E468–E474. CrossRefPubMedGoogle Scholar
  123. 123.
    Lisak RP, Benjamins JA (2017) Melanocortins, melanocortin receptors and multiple sclerosis. Brain Sci 7(8).
  124. 124.
    Abdel-Malek ZA, Swope VB, Nordlund JJ (1992) The nature and biological effects of factors responsible for proliferation and differentiation of melanocytes. Pigment Cell Res Suppl 2:43–47PubMedGoogle Scholar
  125. 125.
    Boston BA (1999) The role of melanocortins in adipocyte function. Ann N Y Acad Sci 885:75–84CrossRefPubMedGoogle Scholar
  126. 126.
    Chhajlani V (1996) Distribution of cDNA for melanocortin receptor subtypes in human tissues. Biochem Mol Biol Int 38(1):73–80PubMedGoogle Scholar
  127. 127.
    Taherzadeh S, Sharma S, Chhajlani V, Gantz I, Rajora N, Demitri MT, Kelly L, Zhao H, Ichiyama T, Catania A, Lipton JM (1999) Alpha-MSH and its receptors in regulation of tumor necrosis factor-alpha production by human monocyte/macrophages. Am J Phys 276(5 Pt 2):R1289–R1294Google Scholar
  128. 128.
    Catania A, Gatti S, Colombo G, Lipton JM (2004) Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol Rev 56(1):1–29. CrossRefPubMedGoogle Scholar
  129. 129.
    Lasaga M, Debeljuk L, Durand D, Scimonelli TN, Caruso C (2008) Role of alpha-melanocyte stimulating hormone and melanocortin 4 receptor in brain inflammation. Peptides 29(10):1825–1835. CrossRefPubMedGoogle Scholar
  130. 130.
    Meder W, Wendland M, Busmann A, Kutzleb C, Spodsberg N, John H, Richter R, Schleuder D, Meyer M, Forssmann WG (2003) Characterization of human circulating TIG2 as a ligand for the orphan receptor ChemR23. FEBS Lett 555(3):495–499CrossRefPubMedGoogle Scholar
  131. 131.
    Vermi W, Riboldi E, Wittamer V, Gentili F, Luini W, Marrelli S, Vecchi A, Franssen JD, Communi D, Massardi L, Sironi M, Mantovani A, Parmentier M, Facchetti F, Sozzani S (2005) Role of ChemR23 in directing the migration of myeloid and plasmacytoid dendritic cells to lymphoid organs and inflamed skin. J Exp Med 201(4):509–515. CrossRefPubMedPubMedCentralGoogle Scholar
  132. 132.
    Nagpal S, Patel S, Jacobe H, DiSepio D, Ghosn C, Malhotra M, Teng M, Duvic M, Chandraratna RA (1997) Tazarotene-induced gene 2 (TIG2), a novel retinoid-responsive gene in skin. J Invest Dermatol 109(1):91–95CrossRefPubMedGoogle Scholar
  133. 133.
    Mariani F, Roncucci L (2015) Chemerin/chemR23 axis in inflammation onset and resolution. Inflammation research : official journal of the European Histamine Research Society [et al] 64(2):85–95. CrossRefGoogle Scholar
  134. 134.
    Wittamer V, Bondue B, Guillabert A, Vassart G, Parmentier M, Communi D (2005) Neutrophil-mediated maturation of chemerin: a link between innate and adaptive immunity. J Immunol 175(1):487–493CrossRefPubMedGoogle Scholar
  135. 135.
    Zabel BA, Allen SJ, Kulig P, Allen JA, Cichy J, Handel TM, Butcher EC (2005) Chemerin activation by serine proteases of the coagulation, fibrinolytic, and inflammatory cascades. J Biol Chem 280(41):34661–34666. CrossRefPubMedGoogle Scholar
  136. 136.
    Parolini S, Santoro A, Marcenaro E, Luini W, Massardi L, Facchetti F, Communi D, Parmentier M, Majorana A, Sironi M, Tabellini G, Moretta A, Sozzani S (2007) The role of chemerin in the colocalization of NK and dendritic cell subsets into inflamed tissues. Blood 109(9):3625–3632. CrossRefPubMedGoogle Scholar
  137. 137.
    Du XY, Zabel BA, Myles T, Allen SJ, Handel TM, Lee PP, Butcher EC, Leung LL (2009) Regulation of chemerin bioactivity by plasma carboxypeptidase N, carboxypeptidase B (activated thrombin-activable fibrinolysis inhibitor), and platelets. J Biol Chem 284(2):751–758. CrossRefPubMedPubMedCentralGoogle Scholar
  138. 138.
    Guillabert A, Wittamer V, Bondue B, Godot V, Imbault V, Parmentier M, Communi D (2008) Role of neutrophil proteinase 3 and mast cell chymase in chemerin proteolytic regulation. J Leukoc Biol 84(6):1530–1538. CrossRefPubMedGoogle Scholar
  139. 139.
    Cash JL, Hart R, Russ A, Dixon JP, Colledge WH, Doran J, Hendrick AG, Carlton MB, Greaves DR (2008) Synthetic chemerin-derived peptides suppress inflammation through ChemR23. J Exp Med 205(4):767–775. CrossRefPubMedPubMedCentralGoogle Scholar
  140. 140.
    Cash JL, Christian AR, Greaves DR (2010) Chemerin peptides promote phagocytosis in a ChemR23- and Syk-dependent manner. J Immunol 184(9):5315–5324. CrossRefPubMedPubMedCentralGoogle Scholar
  141. 141.
    Cash JL, Bass MD, Campbell J, Barnes M, Kubes P, Martin P (2014) Resolution mediator chemerin15 reprograms the wound microenvironment to promote repair and reduce scarring. Curr Biol 24(12):1435. CrossRefPubMedPubMedCentralGoogle Scholar
  142. 142.
    Cash JL, Bena S, Headland SE, McArthur S, Brancaleone V, Perretti M (2013) Chemerin15 inhibits neutrophil-mediated vascular inflammation and myocardial ischemia-reperfusion injury through ChemR23. EMBO Rep 14(11):999–1007. CrossRefPubMedPubMedCentralGoogle Scholar
  143. 143.
    Zhao L, Yang W, Yang X, Lin Y, Lv J, Dou X, Luo Q, Dong J, Chen Z, Chu Y, He R (2014) Chemerin suppresses murine allergic asthma by inhibiting CCL2 production and subsequent airway recruitment of inflammatory dendritic cells. Allergy 69(6):763–774. CrossRefPubMedGoogle Scholar
  144. 144.
    Luangsay S, Wittamer V, Bondue B, De Henau O, Rouger L, Brait M, Franssen JD, de Nadai P, Huaux F, Parmentier M (2009) Mouse ChemR23 is expressed in dendritic cell subsets and macrophages, and mediates an anti-inflammatory activity of chemerin in a lung disease model. J Immunol 183(10):6489–6499. CrossRefPubMedGoogle Scholar
  145. 145.
    van Kooyk Y, Rabinovich GA (2008) Protein-glycan interactions in the control of innate and adaptive immune responses. Nat Immunol 9(6):593–601. CrossRefPubMedGoogle Scholar
  146. 146.
    Rabinovich GA, Ariel A, Hershkoviz R, Hirabayashi J, Kasai KI, Lider O (1999) Specific inhibition of T-cell adhesion to extracellular matrix and proinflammatory cytokine secretion by human recombinant galectin-1. Immunology 97(1):100–106CrossRefPubMedPubMedCentralGoogle Scholar
  147. 147.
    Rabinovich GA, Toscano MA, Jackson SS, Vasta GR (2007) Functions of cell surface galectin-glycoprotein lattices. Curr Opin Struct Biol 17(5):513–520. CrossRefPubMedPubMedCentralGoogle Scholar
  148. 148.
    Rabinovich GA, Toscano MA (2009) Turning 'sweet' on immunity: galectin-glycan interactions in immune tolerance and inflammation. Nat Rev Immunol 9(5):338–352. CrossRefPubMedGoogle Scholar
  149. 149.
    van der Hoeven NW, Hollander MR, Yildirim C, Jansen MF, Teunissen PF, Horrevoets AJ, van der Pouw Kraan TC, van Royen N (2016) The emerging role of galectins in cardiovascular disease. Vasc Pharmacol 81:31–41. CrossRefGoogle Scholar
  150. 150.
    Yang Z, Chiang CK, Chang HT (2008) Synthesis of fluorescent and photovoltaic Cu(2)O nanocubes. Nanotechnology 19(2):025604. CrossRefPubMedGoogle Scholar
  151. 151.
    Mendez-Huergo SP, Blidner AG, Rabinovich GA (2017) Galectins: emerging regulatory checkpoints linking tumor immunity and angiogenesis. Curr Opin Immunol 45:8–15. CrossRefPubMedGoogle Scholar
  152. 152.
    Nio-Kobayashi J (2017) Tissue- and cell-specific localization of galectins, beta-galactose-binding animal lectins, and their potential functions in health and disease. Anat Sci Int 92(1):25–36. CrossRefPubMedGoogle Scholar
  153. 153.
    Sanchez-Cuellar S, de la Fuente H, Cruz-Adalia A, Lamana A, Cibrian D, Giron RM, Vara A, Sanchez-Madrid F, Ancochea J (2012) Reduced expression of galectin-1 and galectin-9 by leucocytes in asthma patients. Clin Exp Immunol 170(3):365–374. CrossRefPubMedPubMedCentralGoogle Scholar
  154. 154.
    Golden-Mason L, Rosen HR (2017) Galectin-9: diverse roles in hepatic immune homeostasis and inflammation. Hepatology 66(1):271–279. CrossRefPubMedPubMedCentralGoogle Scholar
  155. 155.
    Cooper D, Iqbal AJ, Gittens BR, Cervone C, Perretti M (2012) The effect of galectins on leukocyte trafficking in inflammation: sweet or sour? Ann N Y Acad Sci 1253:181–192. CrossRefPubMedGoogle Scholar
  156. 156.
    Rabinovich GA, Baum LG, Tinari N, Paganelli R, Natoli C, Liu FT, Iacobelli S (2002) Galectins and their ligands: amplifiers, silencers or tuners of the inflammatory response? Trends Immunol 23(6):313–320CrossRefPubMedGoogle Scholar
  157. 157.
    Rao SP, Ge XN, Sriramarao P (2017) Regulation of eosinophil recruitment and activation by galectins in allergic asthma. Front Med (Lausanne) 4:68. CrossRefGoogle Scholar
  158. 158.
    Rabinovich GA, Croci DO (2012) Regulatory circuits mediated by lectin-glycan interactions in autoimmunity and cancer. Immunity 36(3):322–335. CrossRefPubMedGoogle Scholar
  159. 159.
    Tsuchiyama Y, Wada J, Zhang H, Morita Y, Hiragushi K, Hida K, Shikata K, Yamamura M, Kanwar YS, Makino H (2000) Efficacy of galectins in the amelioration of nephrotoxic serum nephritis in Wistar Kyoto rats. Kidney Int 58(5):1941–1952. CrossRefPubMedGoogle Scholar
  160. 160.
    Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ, Zheng XX, Strom TB, Kuchroo VK (2005) The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol 6(12):1245–1252. CrossRefPubMedGoogle Scholar
  161. 161.
    Katoh S, Ishii N, Nobumoto A, Takeshita K, Dai SY, Shinonaga R, Niki T, Nishi N, Tominaga A, Yamauchi A, Hirashima M (2007) Galectin-9 inhibits CD44-hyaluronan interaction and suppresses a murine model of allergic asthma. Am J Respir Crit Care Med 176(1):27–35. CrossRefPubMedGoogle Scholar
  162. 162.
    Iqbal AJ, Sampaio AL, Maione F, Greco KV, Niki T, Hirashima M, Perretti M, Cooper D (2011) Endogenous galectin-1 and acute inflammation: emerging notion of a galectin-9 pro-resolving effect. Am J Pathol 178(3):1201–1209. CrossRefPubMedPubMedCentralGoogle Scholar
  163. 163.
    Gil CD, Gullo CE, Oliani SM (2010) Effect of exogenous galectin-1 on leukocyte migration: modulation of cytokine levels and adhesion molecules. Int J Clin Exp Pathol 4(1):74–84PubMedPubMedCentralGoogle Scholar
  164. 164.
    Hsu YL, Wang MY, Ho LJ, Huang CY, Lai JH (2015) Up-regulation of galectin-9 induces cell migration in human dendritic cells infected with dengue virus. J Cell Mol Med 19(5):1065–1076. CrossRefPubMedPubMedCentralGoogle Scholar
  165. 165.
    Wallace JL, Ianaro A, Flannigan KL, Cirino G (2015) Gaseous mediators in resolution of inflammation. Semin Immunol 27(3):227–233. CrossRefPubMedGoogle Scholar
  166. 166.
    Abe K, Kimura H (1996) The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci 16(3):1066–1071CrossRefPubMedGoogle Scholar
  167. 167.
    Hosoki R, Matsuki N, Kimura H (1997) The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide. Biochem Biophys Res Commun 237(3):527–531. CrossRefPubMedGoogle Scholar
  168. 168.
    Stipanuk MH, Beck PW (1982) Characterization of the enzymic capacity for cysteine desulphhydration in liver and kidney of the rat. Biochem J 206(2):267–277CrossRefPubMedPubMedCentralGoogle Scholar
  169. 169.
    Zhao W, Zhang J, Lu Y, Wang R (2001) The vasorelaxant effect of H(2)S as a novel endogenous gaseous K(ATP) channel opener. EMBO J 20(21):6008–6016. CrossRefPubMedPubMedCentralGoogle Scholar
  170. 170.
    Shibuya N, Tanaka M, Yoshida M, Ogasawara Y, Togawa T, Ishii K, Kimura H (2009) 3-Mercaptopyruvate sulfurtransferase produces hydrogen sulfide and bound sulfane sulfur in the brain. Antioxid Redox Signal 11(4):703–714. CrossRefPubMedGoogle Scholar
  171. 171.
    Wallace JL, Ianaro A, de Nucci G (2017) Gaseous mediators in gastrointestinal mucosal defense and injury. Dig Dis Sci.
  172. 172.
    Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288(5789):373–376CrossRefPubMedGoogle Scholar
  173. 173.
    Taylor EL, Megson IL, Haslett C, Rossi AG (2003) Nitric oxide: a key regulator of myeloid inflammatory cell apoptosis. Cell Death Differ 10(4):418–430. CrossRefPubMedGoogle Scholar
  174. 174.
    Kobayashi Y (2010) The regulatory role of nitric oxide in proinflammatory cytokine expression during the induction and resolution of inflammation. J Leukoc Biol 88(6):1157–1162. CrossRefPubMedGoogle Scholar
  175. 175.
    Antonioli L, Csoka B, Fornai M, Colucci R, Kokai E, Blandizzi C, Hasko G (2014) Adenosine and inflammation: what's new on the horizon? Drug Discov Today 19(8):1051–1068. CrossRefPubMedGoogle Scholar
  176. 176.
    de Oliveira Bravo M, Carvalho JL, Saldanha-Araujo F (2016) Adenosine production: a common path for mesenchymal stem-cell and regulatory T-cell-mediated immunosuppression. Purinergic Signal 12(4):595–609. CrossRefPubMedPubMedCentralGoogle Scholar
  177. 177.
    Hasko G, Cronstein B (2013) Regulation of inflammation by adenosine. Front Immunol 4:85. CrossRefPubMedPubMedCentralGoogle Scholar
  178. 178.
    Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50(3):413–492PubMedGoogle Scholar
  179. 179.
    Linden J (2006) New insights into the regulation of inflammation by adenosine. J Clin Invest 116(7):1835–1837. CrossRefPubMedPubMedCentralGoogle Scholar
  180. 180.
    Theron AJ, Steel HC, Tintinger GR, Anderson R (2002) Endogenous adenosine regulates neutrophil pro-inflammatory activities by cyclic AMP-dependent accelerated clearance of cytosolic calcium. Inflammation research : official journal of the European Histamine Research Society [et al] 51(12):594–602CrossRefGoogle Scholar
  181. 181.
    Sun WC, Moore JN, Hurley DJ, Vandenplas ML, Linden J, Cao Z, Murray TF (2008) Adenosine A2A receptor agonists inhibit lipopolysaccharide-induced production of tumor necrosis factor-alpha by equine monocytes. Vet Immunol Immunopathol 121(1–2):91–100. CrossRefPubMedGoogle Scholar
  182. 182.
    Hasko G, Szabo C, Nemeth ZH, Kvetan V, Pastores SM, Vizi ES (1996) Adenosine receptor agonists differentially regulate IL-10, TNF-alpha, and nitric oxide production in RAW 264.7 macrophages and in endotoxemic mice. J Immunol 157(10):4634–4640PubMedGoogle Scholar
  183. 183.
    Hasko G, Kuhel DG, Chen JF, Schwarzschild MA, Deitch EA, Mabley JG, Marton A, Szabo C (2000) Adenosine inhibits IL-12 and TNF-[alpha] production via adenosine A2a receptor-dependent and independent mechanisms. FASEB J 14(13):2065–2074. CrossRefPubMedGoogle Scholar
  184. 184.
    Koscso B, Trepakov A, Csoka B, Nemeth ZH, Pacher P, Eltzschig HK, Hasko G (2013) Stimulation of A2B adenosine receptors protects against trauma-hemorrhagic shock-induced lung injury. Purinergic Signal 9(3):427–432. CrossRefPubMedPubMedCentralGoogle Scholar
  185. 185.
    Csoka B, Selmeczy Z, Koscso B, Nemeth ZH, Pacher P, Murray PJ, Kepka-Lenhart D, Morris SM Jr, Gause WC, Leibovich SJ, Hasko G (2012) Adenosine promotes alternative macrophage activation via A2A and A2B receptors. FASEB J 26(1):376–386. CrossRefPubMedPubMedCentralGoogle Scholar
  186. 186.
    Nemeth ZH, Lutz CS, Csoka B, Deitch EA, Leibovich SJ, Gause WC, Tone M, Pacher P, Vizi ES, Hasko G (2005) Adenosine augments IL-10 production by macrophages through an A2B receptor-mediated posttranscriptional mechanism. J Immunol 175(12):8260–8270CrossRefPubMedPubMedCentralGoogle Scholar
  187. 187.
    Murphree LJ, Sullivan GW, Marshall MA, Linden J (2005) Lipopolysaccharide rapidly modifies adenosine receptor transcripts in murine and human macrophages: role of NF-kappaB in A(2A) adenosine receptor induction. Biochem J 391(Pt 3):575–580. CrossRefPubMedPubMedCentralGoogle Scholar
  188. 188.
    Csoka B, Nemeth ZH, Virag L, Gergely P, Leibovich SJ, Pacher P, Sun CX, Blackburn MR, Vizi ES, Deitch EA, Hasko G (2007) A2A adenosine receptors and C/EBPbeta are crucially required for IL-10 production by macrophages exposed to Escherichia coli. Blood 110(7):2685–2695. CrossRefPubMedPubMedCentralGoogle Scholar
  189. 189.
    Ernens I, Leonard F, Vausort M, Rolland-Turner M, Devaux Y, Wagner DR (2010) Adenosine up-regulates vascular endothelial growth factor in human macrophages. Biochem Biophys Res Commun 392(3):351–356. CrossRefPubMedGoogle Scholar
  190. 190.
    Schnurr M, Toy T, Shin A, Hartmann G, Rothenfusser S, Soellner J, Davis ID, Cebon J, Maraskovsky E (2004) Role of adenosine receptors in regulating chemotaxis and cytokine production of plasmacytoid dendritic cells. Blood 103(4):1391–1397. CrossRefPubMedGoogle Scholar
  191. 191.
    Koshiba M, Rosin DL, Hayashi N, Linden J, Sitkovsky MV (1999) Patterns of A2A extracellular adenosine receptor expression in different functional subsets of human peripheral T cells. Flow cytometry studies with anti-A2A receptor monoclonal antibodies. Mol Pharmacol 55(3):614–624PubMedGoogle Scholar
  192. 192.
    Adair TH (2005) Growth regulation of the vascular system: an emerging role for adenosine. Am J Physiol Regul Integr Comp Physiol 289(2):R283–R296. CrossRefPubMedGoogle Scholar
  193. 193.
    Deaglio S, Dwyer KM, Gao W, Friedman D, Usheva A, Erat A, Chen JF, Enjyoji K, Linden J, Oukka M, Kuchroo VK, Strom TB, Robson SC (2007) Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med 204(6):1257–1265. CrossRefPubMedPubMedCentralGoogle Scholar
  194. 194.
    Pavlov VA, Tracey KJ (2012) The vagus nerve and the inflammatory reflex--linking immunity and metabolism. Nat Rev Endocrinol 8(12):743–754. CrossRefPubMedPubMedCentralGoogle Scholar
  195. 195.
    Andersson U, Tracey KJ (2012) Reflex principles of immunological homeostasis. Annu Rev Immunol 30:313–335. CrossRefPubMedPubMedCentralGoogle Scholar
  196. 196.
    Tracey KJ (2009) Reflex control of immunity. Nat Rev Immunol 9(6):418–428. CrossRefPubMedPubMedCentralGoogle Scholar
  197. 197.
    Chavan SS, Pavlov VA, Tracey KJ (2017) Mechanisms and therapeutic relevance of neuro-immune communication. Immunity 46(6):927–942. CrossRefPubMedPubMedCentralGoogle Scholar
  198. 198.
    Chavan SS, Tracey KJ (2017) Essential Neuroscience in Immunology. J Immunol 198(9):3389–3397. CrossRefPubMedPubMedCentralGoogle Scholar
  199. 199.
    Kawashima K, Fujii T, Moriwaki Y, Misawa H, Horiguchi K (2015) Non-neuronal cholinergic system in regulation of immune function with a focus on alpha7 nAChRs. Int Immunopharmacol 29(1):127–134. CrossRefPubMedGoogle Scholar
  200. 200.
    Rosas-Ballina M, Olofsson PS, Ochani M, Valdes-Ferrer SI, Levine YA, Reardon C, Tusche MW, Pavlov VA, Andersson U, Chavan S, Mak TW, Tracey KJ (2011) Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science 334(6052):98–101. CrossRefPubMedPubMedCentralGoogle Scholar
  201. 201.
    Marino F, Cosentino M (2013) Adrenergic modulation of immune cells: an update. Amino Acids 45(1):55–71. CrossRefPubMedGoogle Scholar
  202. 202.
    Olofsson PS, Katz DA, Rosas-Ballina M, Levine YA, Ochani M, Valdes-Ferrer SI, Pavlov VA, Tracey KJ, Chavan SS (2012) alpha7 nicotinic acetylcholine receptor (alpha7nAChR) expression in bone marrow-derived non-T cells is required for the inflammatory reflex. Mol Med 18:539–543. CrossRefPubMedGoogle Scholar
  203. 203.
    Mirakaj V, Thix CA, Laucher S, Mielke C, Morote-Garcia JC, Schmit MA, Henes J, Unertl KE, Kohler D, Rosenberger P (2010) Netrin-1 dampens pulmonary inflammation during acute lung injury. Am J Respir Crit Care Med 181(8):815–824. CrossRefPubMedGoogle Scholar
  204. 204.
    Aherne CM, Collins CB, Masterson JC, Tizzano M, Boyle TA, Westrich JA, Parnes JA, Furuta GT, Rivera-Nieves J, Eltzschig HK (2012) Neuronal guidance molecule netrin-1 attenuates inflammatory cell trafficking during acute experimental colitis. Gut 61(5):695–705. CrossRefPubMedGoogle Scholar
  205. 205.
    Sun Y, Huang P (2016) Adenosine A2B receptor: from cell biology to human diseases. Front Chem 4:37. CrossRefPubMedPubMedCentralGoogle Scholar
  206. 206.
    Forman HJ, Torres M, Fukuto J (2002) Redox signaling. Mol Cell Biochem 234–235(1–2):49–62CrossRefPubMedGoogle Scholar
  207. 207.
    Leavy O (2014) Inflammation: regulating ROS. Nat Rev Immunol 14(6):357. CrossRefPubMedGoogle Scholar
  208. 208.
    Kuijpers T, Lutter R (2012) Inflammation and repeated infections in CGD: two sides of a coin. Cell Mol Life Sci 69(1):7–15. CrossRefPubMedGoogle Scholar
  209. 209.
    Yasui K, Baba A (2006) Therapeutic potential of superoxide dismutase (SOD) for resolution of inflammation. Inflammation research : official journal of the European Histamine Research Society [et al] 55(9):359–363. CrossRefGoogle Scholar
  210. 210.
    Reis AC, Alessandri AL, Athayde RM, Perez DA, Vago JP, Avila TV, Ferreira TP, de Arantes AC, Coutinho Dde S, Rachid MA, Sousa LP, Martins MA, Menezes GB, Rossi AG, Teixeira MM, Pinho V (2015) Induction of eosinophil apoptosis by hydrogen peroxide promotes the resolution of allergic inflammation. Cell Death Dis 6:e1632. CrossRefPubMedPubMedCentralGoogle Scholar
  211. 211.
    Lopes F, Coelho FM, Costa VV, Vieira EL, Sousa LP, Silva TA, Vieira LQ, Teixeira MM, Pinho V (2011) Resolution of neutrophilic inflammation by H2O2 in antigen-induced arthritis. Arthritis Rheum 63(9):2651–2660. CrossRefPubMedGoogle Scholar
  212. 212.
    Hussain S, Thomassen LC, Ferecatu I, Borot MC, Andreau K, Martens JA, Fleury J, Baeza-Squiban A, Marano F, Boland S (2010) Carbon black and titanium dioxide nanoparticles elicit distinct apoptotic pathways in bronchial epithelial cells. Part Fibre Toxicol 7:10. CrossRefPubMedPubMedCentralGoogle Scholar
  213. 213.
    Fang WT, Li HJ, Zhou LS (2010) Protective effects of prostaglandin E1 on human umbilical vein endothelial cell injury induced by hydrogen peroxide. Acta Pharmacol Sin 31(4):485–492. CrossRefPubMedPubMedCentralGoogle Scholar
  214. 214.
    Kim SJ, Jung HJ, Hyun DH, Park EH, Kim YM, Lim CJ (2010) Glutathione reductase plays an anti-apoptotic role against oxidative stress in human hepatoma cells. Biochimie 92(8):927–932. CrossRefPubMedGoogle Scholar
  215. 215.
    Wang Y, Park KD, Salome C, Wilson SM, Stables JP, Liu R, Khanna R, Kohn H (2011) Development and characterization of novel derivatives of the antiepileptic drug lacosamide that exhibit far greater enhancement in slow inactivation of voltage-gated sodium channels. ACS Chem Neurosci 2(2):90–106. CrossRefPubMedGoogle Scholar
  216. 216.
    Morgan MJ, Liu ZG (2011) Crosstalk of reactive oxygen species and NF-kappaB signaling. Cell Res 21(1):103–115. CrossRefPubMedGoogle Scholar
  217. 217.
    Clempus RE, Griendling KK (2006) Reactive oxygen species signaling in vascular smooth muscle cells. Cardiovasc Res 71(2):216–225. CrossRefPubMedPubMedCentralGoogle Scholar
  218. 218.
    Alessandri AL, Duffin R, Leitch AE, Lucas CD, Sheldrake TA, Dorward DA, Hirani N, Pinho V, de Sousa LP, Teixeira MM, Lyons JF, Haslett C, Rossi AG (2011) Induction of eosinophil apoptosis by the cyclin-dependent kinase inhibitor AT7519 promotes the resolution of eosinophil-dominant allergic inflammation. PLoS One 6(9):e25683. CrossRefPubMedPubMedCentralGoogle Scholar
  219. 219.
    Vago JP, Nogueira CR, Tavares LP, Soriani FM, Lopes F, Russo RC, Pinho V, Teixeira MM, Sousa LP (2012) Annexin A1 modulates natural and glucocorticoid-induced resolution of inflammation by enhancing neutrophil apoptosis. J Leukoc Biol 92(2):249–258. CrossRefPubMedGoogle Scholar
  220. 220.
    Vago JP, Tavares LP, Garcia CC, Lima KM, Perucci LO, Vieira EL, Nogueira CR, Soriani FM, Martins JO, Silva PM, Gomes KB, Pinho V, Bruscoli S, Riccardi C, Beaulieu E, Morand EF, Teixeira MM, Sousa LP (2015) The role and effects of glucocorticoid-induced leucine zipper in the context of inflammation resolution. J Immunol 194(10):4940–4950. CrossRefPubMedGoogle Scholar
  221. 221.
    Vago JP, Tavares LP, Sugimoto MA, Lima GL, Galvao I, de Caux TR, Lima KM, Ribeiro AL, Carneiro FS, Nunes FF, Pinho V, Perretti M, Teixeira MM, Sousa LP (2016) Proresolving actions of synthetic and natural protease inhibitors are mediated by annexin A1. J Immunol 196(4):1922–1932. CrossRefPubMedGoogle Scholar
  222. 222.
    Dalli J, Colas RA, Arnardottir H, Serhan CN (2017) Vagal regulation of group 3 innate lymphoid cells and the immunoresolvent PCTR1 controls infection resolution. Immunity 46(1):92–105. CrossRefPubMedPubMedCentralGoogle Scholar
  223. 223.
    Serhan CN, Chiang N, Dalli J, Levy BD (2014) Lipid mediators in the resolution of inflammation. Cold Spring Harb Perspect Biol 7(2):a016311. CrossRefPubMedGoogle Scholar
  224. 224.
    de Luis D, Domingo JC, Izaola O, Casanueva FF, Bellido D, Sajoux I (2016) Effect of DHA supplementation in a very low-calorie ketogenic diet in the treatment of obesity: a randomized clinical trial. Endocrine 54(1):111–122. CrossRefPubMedGoogle Scholar
  225. 225.
    Lukiw WJ, Bazan NG (2010) Inflammatory, apoptotic, and survival gene signaling in Alzheimer's disease. A review on the bioactivity of neuroprotectin D1 and apoptosis. Mol Neurobiol 42(1):10–16. CrossRefPubMedGoogle Scholar
  226. 226.
    Grenon SM, Owens CD, Nosova EV, Hughes-Fulford M, Alley HF, Chong K, Perez S, Yen PK, Boscardin J, Hellmann J, Spite M, Conte MS (2015) Short-term, high-dose fish oil supplementation increases the production of omega-3 fatty acid-derived mediators in patients with peripheral artery disease (the OMEGA-PAD I trial). J Am Heart Assoc 4(8):e002034. CrossRefPubMedPubMedCentralGoogle Scholar
  227. 227.
    Perucci LO, Sugimoto MA, Gomes KB, Dusse LM, Teixeira MM, Sousa LP (2017) Annexin A1 and specialized proresolving lipid mediators: promoting resolution as a therapeutic strategy in human inflammatory diseases. Expert Opin Ther Targets 21(9):879–896. CrossRefPubMedGoogle Scholar
  228. 228.
    Oliveira LG, Souza-Testasicca MC, Vago JP, Figueiredo AB, Canavaci AM, Perucci LO, Ferreira TP, Coelho EA, Goncalves DU, Rocha MO, PM ES, Ferreira CN, Queiroz-Junior C, Sousa LP, Fernandes AP (2017) Annexin A1 is involved in the resolution of inflammatory responses during Leishmania braziliensis infection. J Immunol 198(8):3227–3236. CrossRefPubMedGoogle Scholar
  229. 229.
    Norling LV, Perretti M (2013) The role of omega-3 derived resolvins in arthritis. Curr Opin Pharmacol 13(3):476–481. CrossRefPubMedGoogle Scholar
  230. 230.
    Jones HR, Robb CT, Perretti M, Rossi AG (2016) The role of neutrophils in inflammation resolution. Semin Immunol 28(2):137–145. CrossRefPubMedGoogle Scholar
  231. 231.
    Ahmed TJ, Kaneva MK, Pitzalis C, Cooper D, Perretti M (2014) Resolution of inflammation: examples of peptidergic players and pathways. Drug Discov Today 19(8):1166–1171. CrossRefPubMedGoogle Scholar
  232. 232.
    Lima KM, Vago JP, Caux TR, Negreiros-Lima GL, Sugimoto MA, Tavares LP, Arribada RG, Carmo AAF, Galvao I, Costa BRC, Soriani FM, Pinho V, Solito E, Perretti M, Teixeira MM, Sousa LP (2017) The resolution of acute inflammation induced by cyclic AMP is dependent on annexin A1. J Biol Chem 292(33):13758–13773. CrossRefPubMedPubMedCentralGoogle Scholar
  233. 233.
    Svensson CI, Zattoni M, Serhan CN (2007) Lipoxins and aspirin-triggered lipoxin inhibit inflammatory pain processing. J Exp Med 204(2):245–252. CrossRefPubMedPubMedCentralGoogle Scholar
  234. 234.
    Maddox JF, Colgan SP, Clish CB, Petasis NA, Fokin VV, Serhan CN (1998) Lipoxin B4 regulates human monocyte/neutrophil adherence and motility: design of stable lipoxin B4 analogs with increased biologic activity. FASEB J 12(6):487–494CrossRefPubMedGoogle Scholar
  235. 235.
    Devchand PR, Arita M, Hong S, Bannenberg G, Moussignac RL, Gronert K, Serhan CN (2003) Human ALX receptor regulates neutrophil recruitment in transgenic mice: roles in inflammation and host defense. FASEB J 17(6):652–659. CrossRefPubMedGoogle Scholar
  236. 236.
    Morris T, Stables M, Hobbs A, de Souza P, Colville-Nash P, Warner T, Newson J, Bellingan G, Gilroy DW (2009) Effects of low-dose aspirin on acute inflammatory responses in humans. J Immunol 183(3):2089–2096. CrossRefPubMedGoogle Scholar
  237. 237.
    Reis MB, Pereira PAT, Caetano GF, Leite MN, Galvao AF, Paula-Silva FWG, Frade MAC, Faccioli LH (2017) Lipoxin A4 encapsulated in PLGA microparticles accelerates wound healing of skin ulcers. PLoS One 12(7):e0182381. CrossRefPubMedPubMedCentralGoogle Scholar
  238. 238.
    Soyombo O, Spur BW, Lee TH (1994) Effects of lipoxin A4 on chemotaxis and degranulation of human eosinophils stimulated by platelet-activating factor and N-formyl-L-methionyl-L-leucyl-L-phenylalanine. Allergy 49(4):230–234CrossRefPubMedGoogle Scholar
  239. 239.
    Qiu FH, Devchand PR, Wada K, Serhan CN (2001) Aspirin-triggered lipoxin A4 and lipoxin A4 up-regulate transcriptional corepressor NAB1 in human neutrophils. FASEB J 15(14):2736–2738. CrossRefPubMedGoogle Scholar
  240. 240.
    Hachicha M, Pouliot M, Petasis NA, Serhan CN (1999) Lipoxin (LX)A4 and aspirin-triggered 15-epi-LXA4 inhibit tumor necrosis factor 1alpha-initiated neutrophil responses and trafficking: regulators of a cytokine-chemokine axis. J Exp Med 189(12):1923–1930CrossRefPubMedPubMedCentralGoogle Scholar
  241. 241.
    Karra L, Haworth O, Priluck R, Levy BD, Levi-Schaffer F (2015) Lipoxin B(4) promotes the resolution of allergic inflammation in the upper and lower airways of mice. Mucosal Immunol 8(4):852–862. CrossRefPubMedGoogle Scholar
  242. 242.
    Godson C, Mitchell S, Harvey K, Petasis NA, Hogg N, Brady HR (2000) Cutting edge: lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages. J Immunol 164(4):1663–1667CrossRefPubMedGoogle Scholar
  243. 243.
    Mitchell S, Thomas G, Harvey K, Cottell D, Reville K, Berlasconi G, Petasis NA, Erwig L, Rees AJ, Savill J, Brady HR, Godson C (2002) Lipoxins, aspirin-triggered epi-lipoxins, lipoxin stable analogues, and the resolution of inflammation: stimulation of macrophage phagocytosis of apoptotic neutrophils in vivo. J Am Soc Nephrol 13(10):2497–2507CrossRefPubMedGoogle Scholar
  244. 244.
    Reville K, Crean JK, Vivers S, Dransfield I, Godson C (2006) Lipoxin A4 redistributes myosin IIA and Cdc42 in macrophages: implications for phagocytosis of apoptotic leukocytes. J Immunol 176(3):1878–1888CrossRefPubMedGoogle Scholar
  245. 245.
    Grumbach Y, Quynh NV, Chiron R, Urbach V (2009) LXA4 stimulates ZO-1 expression and transepithelial electrical resistance in human airway epithelial (16HBE14o-) cells. Am J Physiol Lung Cell Mol Physiol 296(1):L101–L108. CrossRefPubMedGoogle Scholar
  246. 246.
    Hawkins KE, DeMars KM, Alexander JC, de Leon LG, Pacheco SC, Graves C, Yang C, McCrea AO, Frankowski JC, Garrett TJ, Febo M, Candelario-Jalil E (2017) Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A4 analog: protective mechanisms and long-term effects on neurological recovery. Brain Behav 7(5):e00688. CrossRefPubMedPubMedCentralGoogle Scholar
  247. 247.
    Barden AE, Moghaddami M, Mas E, Phillips M, Cleland LG, Mori TA (2016) Specialised pro-resolving mediators of inflammation in inflammatory arthritis. Prostaglandins Leukot Essent Fatty Acids 107:24–29. CrossRefPubMedGoogle Scholar
  248. 248.
    Jo YY, Lee JY, Park CK (2016) Resolvin E1 inhibits substance P-induced potentiation of TRPV1 in primary sensory neurons. Mediat Inflamm 2016:5259321. CrossRefGoogle Scholar
  249. 249.
    Tjonahen E, Oh SF, Siegelman J, Elangovan S, Percarpio KB, Hong S, Arita M, Serhan CN (2006) Resolvin E2: identification and anti-inflammatory actions: pivotal role of human 5-lipoxygenase in resolvin E series biosynthesis. Chem Biol 13(11):1193–1202. CrossRefPubMedGoogle Scholar
  250. 250.
    Rajasagi NK, Reddy PB, Mulik S, Gjorstrup P, Rouse BT (2013) Neuroprotectin D1 reduces the severity of herpes simplex virus-induced corneal immunopathology. Invest Ophthalmol Vis Sci 54(9):6269–6279. CrossRefPubMedPubMedCentralGoogle Scholar
  251. 251.
    Rajasagi NK, Reddy PB, Suryawanshi A, Mulik S, Gjorstrup P, Rouse BT (2011) Controlling herpes simplex virus-induced ocular inflammatory lesions with the lipid-derived mediator resolvin E1. J Immunol 186(3):1735–1746. CrossRefPubMedGoogle Scholar
  252. 252.
    Rey C, Nadjar A, Buaud B, Vaysse C, Aubert A, Pallet V, Laye S, Joffre C (2016) Resolvin D1 and E1 promote resolution of inflammation in microglial cells in vitro. Brain Behav Immun 55:249–259. CrossRefPubMedGoogle Scholar
  253. 253.
    Herrera BS, Hasturk H, Kantarci A, Freire MO, Nguyen O, Kansal S, Van Dyke TE (2015) Impact of resolvin E1 on murine neutrophil phagocytosis in type 2 diabetes. Infect Immun 83(2):792–801. CrossRefPubMedPubMedCentralGoogle Scholar
  254. 254.
    Hasturk H, Kantarci A, Ohira T, Arita M, Ebrahimi N, Chiang N, Petasis NA, Levy BD, Serhan CN, Van Dyke TE (2006) RvE1 protects from local inflammation and osteoclast- mediated bone destruction in periodontitis. FASEB J 20(2):401–403. CrossRefPubMedGoogle Scholar
  255. 255.
    Hasturk H, Kantarci A, Goguet-Surmenian E, Blackwood A, Andry C, Serhan CN, Van Dyke TE (2007) Resolvin E1 regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo. J Immunol 179(10):7021–7029CrossRefPubMedGoogle Scholar
  256. 256.
    Aoki H, Hisada T, Ishizuka T, Utsugi M, Kawata T, Shimizu Y, Okajima F, Dobashi K, Mori M (2008) Resolvin E1 dampens airway inflammation and hyperresponsiveness in a murine model of asthma. Biochem Biophys Res Commun 367(2):509–515. CrossRefPubMedGoogle Scholar
  257. 257.
    Lee CT, Teles R, Kantarci A, Chen T, McCafferty J, Starr JR, Brito LC, Paster BJ, Van Dyke TE (2016) Resolvin E1 reverses experimental periodontitis and dysbiosis. J Immunol 197(7):2796–2806. CrossRefPubMedPubMedCentralGoogle Scholar
  258. 258.
    Salic K, Morrison MC, Verschuren L, Wielinga PY, Wu L, Kleemann R, Gjorstrup P, Kooistra T (2016) Resolvin E1 attenuates atherosclerosis in absence of cholesterol-lowering effects and on top of atorvastatin. Atherosclerosis 250:158–165. CrossRefPubMedGoogle Scholar
  259. 259.
    Dona M, Fredman G, Schwab JM, Chiang N, Arita M, Goodarzi A, Cheng G, von Andrian UH, Serhan CN (2008) Resolvin E1, an EPA-derived mediator in whole blood, selectively counterregulates leukocytes and platelets. Blood 112(3):848–855. CrossRefPubMedPubMedCentralGoogle Scholar
  260. 260.
    Bang S, Yoo S, Yang TJ, Cho H, Kim YG, Hwang SW (2010) Resolvin D1 attenuates activation of sensory transient receptor potential channels leading to multiple anti-nociception. Br J Pharmacol 161(3):707–720. CrossRefPubMedPubMedCentralGoogle Scholar
  261. 261.
    Quan-Xin F, Fan F, Xiang-Ying F, Shu-Jun L, Shi-Qi W, Zhao-Xu L, Xu-Jie Z, Qing-Chuan Z, Wei W (2012) Resolvin D1 reverses chronic pancreatitis-induced mechanical allodynia, phosphorylation of NMDA receptors, and cytokines expression in the thoracic spinal dorsal horn. BMC Gastroenterol 12:148. CrossRefPubMedPubMedCentralGoogle Scholar
  262. 262.
    Lima-Garcia JF, Dutra RC, da Silva K, Motta EM, Campos MM, Calixto JB (2011) The precursor of resolvin D series and aspirin-triggered resolvin D1 display anti-hyperalgesic properties in adjuvant-induced arthritis in rats. Br J Pharmacol 164(2):278–293. CrossRefPubMedPubMedCentralGoogle Scholar
  263. 263.
    Oehler B, Mohammadi M, Perpina Viciano C, Hackel D, Hoffmann C, Brack A, Rittner HL (2017) Peripheral interaction of resolvin D1 and E1 with opioid receptor antagonists for antinociception in inflammatory pain in rats. Front Mol Neurosci 10:242. CrossRefPubMedPubMedCentralGoogle Scholar
  264. 264.
    Bento AF, Claudino RF, Dutra RC, Marcon R, Calixto JB (2011) Omega-3 fatty acid-derived mediators 17(R)-hydroxy docosahexaenoic acid, aspirin-triggered resolvin D1 and resolvin D2 prevent experimental colitis in mice. J Immunol 187(4):1957–1969. CrossRefPubMedGoogle Scholar
  265. 265.
    Croasdell A, Thatcher TH, Kottmann RM, Colas RA, Dalli J, Serhan CN, Sime PJ, Phipps RP (2015) Resolvins attenuate inflammation and promote resolution in cigarette smoke-exposed human macrophages. Am J Physiol Lung Cell Mol Physiol 309(8):L888–L901. CrossRefPubMedPubMedCentralGoogle Scholar
  266. 266.
    Xu J, Gao X, Yang C, Chen L, Chen Z (2017) Resolvin D1 attenuates Mpp+-induced Parkinson disease via inhibiting inflammation in PC12 cells. Med Sci Monit 23:2684–2691CrossRefPubMedPubMedCentralGoogle Scholar
  267. 267.
    Yin Y, Chen F, Wang W, Wang H, Zhang X (2017) Resolvin D1 inhibits inflammatory response in STZ-induced diabetic retinopathy rats: possible involvement of NLRP3 inflammasome and NF-kappaB signaling pathway. Mol Vis 23:242–250PubMedPubMedCentralGoogle Scholar
  268. 268.
    Park CK, Lu N, Xu ZZ, Liu T, Serhan CN, Ji RR (2011) Resolving TRPV1- and TNF-alpha-mediated spinal cord synaptic plasticity and inflammatory pain with neuroprotectin D1. The Journal of neuroscience : the official journal of the Society for Neuroscience 31(42):15072–15085. CrossRefGoogle Scholar
  269. 269.
    Bannenberg GL, Chiang N, Ariel A, Arita M, Tjonahen E, Gotlinger KH, Hong S, Serhan CN (2005) Molecular circuits of resolution: formation and actions of resolvins and protectins. J Immunol 174(7):4345–4355CrossRefPubMedGoogle Scholar
  270. 270.
    Duffield JS, Hong S, Vaidya VS, Lu Y, Fredman G, Serhan CN, Bonventre JV (2006) Resolvin D series and protectin D1 mitigate acute kidney injury. J Immunol 177(9):5902–5911CrossRefPubMedGoogle Scholar
  271. 271.
    Ren J, Meng S, Yan B, Yu J, Liu J (2016) Protectin D1 reduces concanavalin A-induced liver injury by inhibiting NF-kappaB-mediated CX3CL1/CX3CR1 axis and NLR family, pyrin domain containing 3 inflammasome activation. Mol Med Rep 13(4):3627–3638. CrossRefPubMedGoogle Scholar
  272. 272.
    Zhu M, Wang X, Hjorth E, Colas RA, Schroeder L, Granholm AC, Serhan CN, Schultzberg M (2016) Pro-resolving lipid mediators improve neuronal survival and increase Abeta42 phagocytosis. Mol Neurobiol 53(4):2733–2749. CrossRefPubMedGoogle Scholar
  273. 273.
    Serhan CN, Chiang N, Dalli J (2015) The resolution code of acute inflammation: novel pro-resolving lipid mediators in resolution. Semin Immunol 27(3):200–215. CrossRefPubMedPubMedCentralGoogle Scholar
  274. 274.
    Colas RA, Dalli J, Chiang N, Vlasakov I, Sanger JM, Riley IR, Serhan CN (2016) Identification and actions of the maresin 1 metabolome in infectious inflammation. J Immunol 197(11):4444–4452. CrossRefPubMedPubMedCentralGoogle Scholar
  275. 275.
    Rius B, Duran-Guell M, Flores-Costa R, Lopez-Vicario C, Lopategi A, Alcaraz-Quiles J, Casulleras M, Lozano JJ, Titos E, Claria J (2017) The specialized pro-resolving lipid mediator maresin 1 protects hepatocytes from lipotoxic and hypoxia-induced endoplasmic reticulum stress. FASEB J.
  276. 276.
    Krishnamoorthy N, Burkett PR, Dalli J, Abdulnour RE, Colas R, Ramon S, Phipps RP, Petasis NA, Kuchroo VK, Serhan CN, Levy BD (2015) Cutting edge: maresin-1 engages regulatory T cells to limit type 2 innate lymphoid cell activation and promote resolution of lung inflammation. J Immunol 194(3):863–867. CrossRefPubMedGoogle Scholar
  277. 277.
    Martinez-Fernandez L, Gonzalez-Muniesa P, Laiglesia LM, Sainz N, Prieto-Hontoria PL, Escote X, Odriozola L, Corrales FJ, Arbones-Mainar JM, Martinez JA, Moreno-Aliaga MJ (2017) Maresin 1 improves insulin sensitivity and attenuates adipose tissue inflammation in ob/ob and diet-induced obese mice. FASEB J 31(5):2135–2145. CrossRefPubMedGoogle Scholar
  278. 278.
    Tang S, Gao C, Long Y, Huang W, Chen J, Fan F, Jiang C, Xu Y (2017) Maresin 1 mitigates high glucose-induced mouse glomerular mesangial cell injury by inhibiting inflammation and fibrosis. Mediat Inflamm 2017:2438247. CrossRefGoogle Scholar
  279. 279.
    Lannan KL, Spinelli SL, Blumberg N, Phipps RP (2017) Maresin 1 induces a novel pro-resolving phenotype in human platelets. J Thromb Haemost 15(4):802–813. CrossRefPubMedPubMedCentralGoogle Scholar
  280. 280.
    Viola JR, Lemnitzer P, Jansen Y, Csaba G, Winter C, Neideck C, Silvestre-Roig C, Dittmar G, Doring Y, Drechsler M, Weber C, Zimmer R, Cenac N, Soehnlein O (2016) Resolving lipid mediators maresin 1 and resolvin D2 prevent atheroprogression in mice. Circ Res 119(9):1030–1038. CrossRefPubMedGoogle Scholar
  281. 281.
    Perretti M, Flower RJ (1993) Modulation of IL-1-induced neutrophil migration by dexamethasone and lipocortin 1. J Immunol 150(3):992–999PubMedGoogle Scholar
  282. 282.
    Lim LH, Solito E, Russo-Marie F, Flower RJ, Perretti M (1998) Promoting detachment of neutrophils adherent to murine postcapillary venules to control inflammation: effect of lipocortin 1. Proc Natl Acad Sci U S A 95(24):14535–14539CrossRefPubMedPubMedCentralGoogle Scholar
  283. 283.
    Walther A, Riehemann K, Gerke V (2000) A novel ligand of the formyl peptide receptor: annexin I regulates neutrophil extravasation by interacting with the FPR. Mol Cell 5(5):831–840CrossRefPubMedGoogle Scholar
  284. 284.
    Hayhoe RP, Kamal AM, Solito E, Flower RJ, Cooper D, Perretti M (2006) Annexin 1 and its bioactive peptide inhibit neutrophil-endothelium interactions under flow: indication of distinct receptor involvement. Blood 107(5):2123–2130. CrossRefPubMedGoogle Scholar
  285. 285.
    Pederzoli-Ribeil M, Maione F, Cooper D, Al-Kashi A, Dalli J, Perretti M, D'Acquisto F (2010) Design and characterization of a cleavage-resistant Annexin A1 mutant to control inflammation in the microvasculature. Blood 116(20):4288–4296. CrossRefPubMedGoogle Scholar
  286. 286.
    McKanna JA (1995) Lipocortin 1 in apoptosis: mammary regression. Anat Rec 242(1):1–10. CrossRefPubMedGoogle Scholar
  287. 287.
    Sakamoto T, Repasky WT, Uchida K, Hirata A, Hirata F (1996) Modulation of cell death pathways to apoptosis and necrosis of H2O2-treated rat thymocytes by lipocortin I. Biochem Biophys Res Commun 220(3):643–647. CrossRefPubMedGoogle Scholar
  288. 288.
    Wang W, Post JI, Dow KE, Shin SH, Riopelle RJ, Ross GM (1999) Zinc and copper inhibit nerve growth factor-mediated protection from oxidative stress-induced apoptosis. Neurosci Lett 259(2):115–118CrossRefPubMedGoogle Scholar
  289. 289.
    Solito E, de Coupade C, Canaider S, Goulding NJ, Perretti M (2001) Transfection of annexin 1 in monocytic cells produces a high degree of spontaneous and stimulated apoptosis associated with caspase-3 activation. Br J Pharmacol 133(2):217–228. CrossRefPubMedPubMedCentralGoogle Scholar
  290. 290.
    Debret R, El Btaouri H, Duca L, Rahman I, Radke S, Haye B, Sallenave JM, Antonicelli F (2003) Annexin A1 processing is associated with caspase-dependent apoptosis in BZR cells. FEBS Lett 546(2–3):195–202CrossRefPubMedGoogle Scholar
  291. 291.
    Maderna P, Yona S, Perretti M, Godson C (2005) Modulation of phagocytosis of apoptotic neutrophils by supernatant from dexamethasone-treated macrophages and annexin-derived peptide Ac(2-26). J Immunol 174(6):3727–3733CrossRefPubMedGoogle Scholar
  292. 292.
    Scannell M, Flanagan MB, deStefani A, Wynne KJ, Cagney G, Godson C, Maderna P (2007) Annexin-1 and peptide derivatives are released by apoptotic cells and stimulate phagocytosis of apoptotic neutrophils by macrophages. J Immunol 178(7):4595–4605CrossRefPubMedGoogle Scholar
  293. 293.
    Blume KE, Soeroes S, Waibel M, Keppeler H, Wesselborg S, Herrmann M, Schulze-Osthoff K, Lauber K (2009) Cell surface externalization of annexin A1 as a failsafe mechanism preventing inflammatory responses during secondary necrosis. J Immunol 183(12):8138–8147. CrossRefPubMedGoogle Scholar
  294. 294.
    Wu CC, Croxtall JD, Perretti M, Bryant CE, Thiemermann C, Flower RJ, Vane JR (1995) Lipocortin 1 mediates the inhibition by dexamethasone of the induction by endotoxin of nitric oxide synthase in the rat. Proc Natl Acad Sci U S A 92(8):3473–3477CrossRefPubMedPubMedCentralGoogle Scholar
  295. 295.
    Minghetti L, Nicolini A, Polazzi E, Greco A, Perretti M, Parente L, Levi G (1999) Down-regulation of microglial cyclo-oxygenase-2 and inducible nitric oxide synthase expression by lipocortin 1. Br J Pharmacol 126(6):1307–1314. CrossRefPubMedPubMedCentralGoogle Scholar
  296. 296.
    Ferlazzo V, D'Agostino P, Milano S, Caruso R, Feo S, Cillari E, Parente L (2003) Anti-inflammatory effects of annexin-1: stimulation of IL-10 release and inhibition of nitric oxide synthesis. Int Immunopharmacol 3(10–11):1363–1369. CrossRefPubMedGoogle Scholar
  297. 297.
    Gavins FN, Dalli J, Flower RJ, Granger DN, Perretti M (2007) Activation of the annexin 1 counter-regulatory circuit affords protection in the mouse brain microcirculation. FASEB J 21(8):1751–1758. CrossRefPubMedGoogle Scholar
  298. 298.
    Martin GR, Perretti M, Flower RJ, Wallace JL (2008) Annexin-1 modulates repair of gastric mucosal injury. Am J Physiol Gastrointest Liver Physiol 294(3):G764–G769. CrossRefPubMedGoogle Scholar
  299. 299.
    Damazo AS, Sampaio AL, Nakata CM, Flower RJ, Perretti M, Oliani SM (2011) Endogenous annexin A1 counter-regulates bleomycin-induced lung fibrosis. BMC Immunol 12:59. CrossRefPubMedPubMedCentralGoogle Scholar
  300. 300.
    Gavins FN, Hughes EL, Buss NA, Holloway PM, Getting SJ, Buckingham JC (2012) Leukocyte recruitment in the brain in sepsis: involvement of the annexin 1-FPR2/ALX anti-inflammatory system. FASEB J 26(12):4977–4989. CrossRefPubMedGoogle Scholar
  301. 301.
    Leoni G, Alam A, Neumann PA, Lambeth JD, Cheng G, McCoy J, Hilgarth RS, Kundu K, Murthy N, Kusters D, Reutelingsperger C, Perretti M, Parkos CA, Neish AS, Nusrat A (2013) Annexin A1, formyl peptide receptor, and NOX1 orchestrate epithelial repair. J Clin Invest 123(1):443–454. CrossRefPubMedGoogle Scholar
  302. 302.
    Locatelli I, Sutti S, Jindal A, Vacchiano M, Bozzola C, Reutelingsperger C, Kusters D, Bena S, Parola M, Paternostro C, Bugianesi E, McArthur S, Albano E, Perretti M (2014) Endogenous annexin A1 is a novel protective determinant in nonalcoholic steatohepatitis in mice. Hepatology 60(2):531–544. CrossRefPubMedPubMedCentralGoogle Scholar
  303. 303.
    Kusters DH, Chatrou ML, Willems BA, De Saint-Hubert M, Bauwens M, van der Vorst E, Bena S, Biessen EA, Perretti M, Schurgers LJ, Reutelingsperger CP (2015) Pharmacological treatment with annexin A1 reduces atherosclerotic plaque burden in LDLR-/- mice on western type diet. PLoS One 10(6):e0130484. CrossRefPubMedPubMedCentralGoogle Scholar
  304. 304.
    Galvao I, Dias AC, Tavares LD, Rodrigues IP, Queiroz-Junior CM, Costa VV, Reis AC, Ribeiro Oliveira RD, Louzada-Junior P, Souza DG, Leng L, Bucala R, Sousa LP, Bozza MT, Teixeira MM, Amaral FA (2016) Macrophage migration inhibitory factor drives neutrophil accumulation by facilitating IL-1beta production in a murine model of acute gout. J Leukoc Biol 99(6):1035–1043. CrossRefPubMedPubMedCentralGoogle Scholar
  305. 305.
    Taylor AW, Streilein JW, Cousins SW (1994) Alpha-melanocyte-stimulating hormone suppresses antigen-stimulated T cell production of gamma-interferon. Neuroimmunomodulation 1(3):188–194CrossRefPubMedGoogle Scholar
  306. 306.
    Lipton JM, Catania A (1997) Anti-inflammatory actions of the neuroimmunomodulator alpha-MSH. Immunol Today 18(3):140–145CrossRefPubMedGoogle Scholar
  307. 307.
    Manna SK, Sarkar A, Sreenivasan Y (2006) Alpha-melanocyte-stimulating hormone down-regulates CXC receptors through activation of neutrophil elastase. Eur J Immunol 36(3):754–769. CrossRefPubMedGoogle Scholar
  308. 308.
    Delgado R, Carlin A, Airaghi L, Demitri MT, Meda L, Galimberti D, Baron P, Lipton JM, Catania A (1998) Melanocortin peptides inhibit production of proinflammatory cytokines and nitric oxide by activated microglia. J Leukoc Biol 63(6):740–745CrossRefPubMedGoogle Scholar
  309. 309.
    Capsoni F, Ongari AM, Reali E, Catania A (2009) Melanocortin peptides inhibit urate crystal-induced activation of phagocytic cells. Arthritis Res Ther 11(5):R151. CrossRefPubMedPubMedCentralGoogle Scholar
  310. 310.
    Kaneva MK, Kerrigan MJ, Grieco P, Curley GP, Locke IC, Getting SJ (2012) Chondroprotective and anti-inflammatory role of melanocortin peptides in TNF-alpha activated human C-20/A4 chondrocytes. Br J Pharmacol 167(1):67–79. CrossRefPubMedPubMedCentralGoogle Scholar
  311. 311.
    Auriemma M, Brzoska T, Klenner L, Kupas V, Goerge T, Voskort M, Zhao Z, Sparwasser T, Luger TA, Loser K (2012) Alpha-MSH-stimulated tolerogenic dendritic cells induce functional regulatory T cells and ameliorate ongoing skin inflammation. J Invest Dermatol 132(7):1814–1824. CrossRefPubMedGoogle Scholar
  312. 312.
    Bhardwaj R, Becher E, Mahnke K, Hartmeyer M, Schwarz T, Scholzen T, Luger TA (1997) Evidence for the differential expression of the functional alpha-melanocyte-stimulating hormone receptor MC-1 on human monocytes. J Immunol 158(7):3378–3384PubMedGoogle Scholar
  313. 313.
    Taylor A, Namba K (2001) In vitro induction of CD25+ CD4+ regulatory T cells by the neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH). Immunol Cell Biol 79(4):358–367. CrossRefPubMedGoogle Scholar
  314. 314.
    Mandrika I, Muceniece R, Wikberg JE (2001) Effects of melanocortin peptides on lipopolysaccharide/interferon-gamma-induced NF-kappaB DNA binding and nitric oxide production in macrophage-like RAW 264.7 cells: evidence for dual mechanisms of action. Biochem Pharmacol 61(5):613–621CrossRefPubMedGoogle Scholar
  315. 315.
    Becher E, Mahnke K, Brzoska T, Kalden DH, Grabbe S, Luger TA (1999) Human peripheral blood-derived dendritic cells express functional melanocortin receptor MC-1R. Ann N Y Acad Sci 885:188–195CrossRefPubMedGoogle Scholar
  316. 316.
    Haycock JW, Wagner M, Morandini R, Ghanem G, Rennie IG, Mac Neil S (1999) Alpha-melanocyte-stimulating hormone inhibits NF-kappaB activation in human melanocytes and melanoma cells. J Invest Dermatol 113(4):560–566. CrossRefPubMedGoogle Scholar
  317. 317.
    Manna SK, Aggarwal BB (1998) Alpha-melanocyte-stimulating hormone inhibits the nuclear transcription factor NF-kappa B activation induced by various inflammatory agents. J Immunol 161(6):2873–2880PubMedGoogle Scholar
  318. 318.
    Galimberti D, Baron P, Meda L, Prat E, Scarpini E, Delgado R, Catania A, Lipton JM, Scarlato G (1999) Alpha-MSH peptides inhibit production of nitric oxide and tumor necrosis factor-alpha by microglial cells activated with beta-amyloid and interferon gamma. Biochem Biophys Res Commun 263(1):251–256. CrossRefPubMedGoogle Scholar
  319. 319.
    Brzoska T, Kalden DH, Scholzen T, Luger TA (1999) Molecular basis of the alpha-MSH/IL-1 antagonism. Ann N Y Acad Sci 885:230–238CrossRefPubMedGoogle Scholar
  320. 320.
    Scholzen TE, Sunderkotter C, Kalden DH, Brzoska T, Fastrich M, Fisbeck T, Armstrong CA, Ansel JC, Luger TA (2003) Alpha-melanocyte stimulating hormone prevents lipopolysaccharide-induced vasculitis by down-regulating endothelial cell adhesion molecule expression. Endocrinology 144(1):360–370. CrossRefPubMedGoogle Scholar
  321. 321.
    Montero-Melendez T, Patel HB, Perretti M (2011) Role of melanocortin receptors in the regulation of gouty inflammation. Curr Rheumatol Rep 13(2):138–145. CrossRefPubMedGoogle Scholar
  322. 322.
    Toscano MA, Bianco GA, Ilarregui JM, Croci DO, Correale J, Hernandez JD, Zwirner NW, Poirier F, Riley EM, Baum LG, Rabinovich GA (2007) Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death. Nat Immunol 8(8):825–834. CrossRefPubMedGoogle Scholar
  323. 323.
    Norling LV, Sampaio AL, Cooper D, Perretti M (2008) Inhibitory control of endothelial galectin-1 on in vitro and in vivo lymphocyte trafficking. FASEB J 22(3):682–690. CrossRefPubMedGoogle Scholar
  324. 324.
    Rabinovich GA, Sotomayor CE, Riera CM, Bianco I, Correa SG (2000) Evidence of a role for galectin-1 in acute inflammation. Eur J Immunol 30(5):1331–1339.<1331::AID-IMMU1331>3.0.CO;2-HCrossRefPubMedGoogle Scholar
  325. 325.
    Correa SG, Sotomayor CE, Aoki MP, Maldonado CA, Rabinovich GA (2003) Opposite effects of galectin-1 on alternative metabolic pathways of L-arginine in resident, inflammatory, and activated macrophages. Glycobiology 13(2):119–128. CrossRefPubMedGoogle Scholar
  326. 326.
    Barrionuevo P, Beigier-Bompadre M, Ilarregui JM, Toscano MA, Bianco GA, Isturiz MA, Rabinovich GA (2007) A novel function for galectin-1 at the crossroad of innate and adaptive immunity: galectin-1 regulates monocyte/macrophage physiology through a nonapoptotic ERK-dependent pathway. J Immunol 178(1):436–445CrossRefPubMedGoogle Scholar
  327. 327.
    Ilarregui JM, Croci DO, Bianco GA, Toscano MA, Salatino M, Vermeulen ME, Geffner JR, Rabinovich GA (2009) Tolerogenic signals delivered by dendritic cells to T cells through a galectin-1-driven immunoregulatory circuit involving interleukin 27 and interleukin 10. Nat Immunol 10(9):981–991. CrossRefPubMedGoogle Scholar
  328. 328.
    van der Leij J, van den Berg A, Harms G, Eschbach H, Vos H, Zwiers P, van Weeghel R, Groen H, Poppema S, Visser L (2007) Strongly enhanced IL-10 production using stable galectin-1 homodimers. Mol Immunol 44(4):506–513. CrossRefPubMedGoogle Scholar
  329. 329.
    Stowell SR, Qian Y, Karmakar S, Koyama NS, Dias-Baruffi M, Leffler H, McEver RP, Cummings RD (2008) Differential roles of galectin-1 and galectin-3 in regulating leukocyte viability and cytokine secretion. J Immunol 180(5):3091–3102CrossRefPubMedGoogle Scholar
  330. 330.
    Cedeno-Laurent F, Barthel SR, Opperman MJ, Lee DM, Clark RA, Dimitroff CJ (2010) Development of a nascent galectin-1 chimeric molecule for studying the role of leukocyte galectin-1 ligands and immune disease modulation. J Immunol 185(8):4659–4672. CrossRefPubMedPubMedCentralGoogle Scholar
  331. 331.
    Rostoker R, Yaseen H, Schif-Zuck S, Lichtenstein RG, Rabinovich GA, Ariel A (2013) Galectin-1 induces 12/15-lipoxygenase expression in murine macrophages and favors their conversion toward a pro-resolving phenotype. Prostaglandins Other Lipid Mediat 107:85–94. CrossRefPubMedGoogle Scholar
  332. 332.
    Katoh S, Nobumoto A, Matsumoto N, Matsumoto K, Ehara N, Niki T, Inada H, Nishi N, Yamauchi A, Fukushima K, Hirashima M (2010) Involvement of galectin-9 in lung eosinophilia in patients with eosinophilic pneumonia. Int Arch Allergy Immunol 153(3):294–302. CrossRefPubMedGoogle Scholar
  333. 333.
    Niki T, Tsutsui S, Hirose S, Aradono S, Sugimoto Y, Takeshita K, Nishi N, Hirashima M (2009) Galectin-9 is a high affinity IgE-binding lectin with anti-allergic effect by blocking IgE-antigen complex formation. J Biol Chem 284(47):32344–32352. CrossRefPubMedPubMedCentralGoogle Scholar
  334. 334.
    Oomizu S, Arikawa T, Niki T, Kadowaki T, Ueno M, Nishi N, Yamauchi A, Hirashima M (2012) Galectin-9 suppresses Th17 cell development in an IL-2-dependent but Tim-3-independent manner. Clin Immunol 143(1):51–58. CrossRefPubMedGoogle Scholar
  335. 335.
    Whiteman M, Armstrong JS, Chu SH, Jia-Ling S, Wong BS, Cheung NS, Halliwell B, Moore PK (2004) The novel neuromodulator hydrogen sulfide: an endogenous peroxynitrite 'scavenger'? J Neurochem 90(3):765–768. CrossRefPubMedGoogle Scholar
  336. 336.
    Whiteman M, Cheung NS, Zhu YZ, Chu SH, Siau JL, Wong BS, Armstrong JS, Moore PK (2005) Hydrogen sulphide: a novel inhibitor of hypochlorous acid-mediated oxidative damage in the brain? Biochem Biophys Res Commun 326(4):794–798. CrossRefPubMedGoogle Scholar
  337. 337.
    Whiteman M, Li L, Rose P, Tan CH, Parkinson DB, Moore PK (2010) The effect of hydrogen sulfide donors on lipopolysaccharide-induced formation of inflammatory mediators in macrophages. Antioxid Redox Signal 12(10):1147–1154. CrossRefPubMedPubMedCentralGoogle Scholar
  338. 338.
    Muzaffar S, Shukla N, Bond M, Newby AC, Angelini GD, Sparatore A, Del Soldato P, Jeremy JY (2008) Exogenous hydrogen sulfide inhibits superoxide formation, NOX-1 expression and Rac1 activity in human vascular smooth muscle cells. J Vasc Res 45(6):521–528. CrossRefPubMedGoogle Scholar
  339. 339.
    Distrutti E, Sediari L, Mencarelli A, Renga B, Orlandi S, Antonelli E, Roviezzo F, Morelli A, Cirino G, Wallace JL, Fiorucci S (2006) Evidence that hydrogen sulfide exerts antinociceptive effects in the gastrointestinal tract by activating KATP channels. J Pharmacol Exp Ther 316(1):325–335. CrossRefPubMedGoogle Scholar
  340. 340.
    Zanardo RC, Brancaleone V, Distrutti E, Fiorucci S, Cirino G, Wallace JL (2006) Hydrogen sulfide is an endogenous modulator of leukocyte-mediated inflammation. FASEB J 20(12):2118–2120. CrossRefPubMedGoogle Scholar
  341. 341.
    Goubern M, Andriamihaja M, Nubel T, Blachier F, Bouillaud F (2007) Sulfide, the first inorganic substrate for human cells. FASEB J 21(8):1699–1706. CrossRefPubMedGoogle Scholar
  342. 342.
    Lagoutte E, Mimoun S, Andriamihaja M, Chaumontet C, Blachier F, Bouillaud F (2010) Oxidation of hydrogen sulfide remains a priority in mammalian cells and causes reverse electron transfer in colonocytes. Biochim Biophys Acta 1797(8):1500–1511. CrossRefPubMedGoogle Scholar
  343. 343.
    Mimoun S, Andriamihaja M, Chaumontet C, Atanasiu C, Benamouzig R, Blouin JM, Tome D, Bouillaud F, Blachier F (2012) Detoxification of H(2)S by differentiated colonic epithelial cells: implication of the sulfide oxidizing unit and of the cell respiratory capacity. Antioxid Redox Signal 17(1):1–10. CrossRefPubMedGoogle Scholar
  344. 344.
    Li L, Rossoni G, Sparatore A, Lee LC, Del Soldato P, Moore PK (2007) Anti-inflammatory and gastrointestinal effects of a novel diclofenac derivative. Free Radic Biol Med 42(5):706–719. CrossRefPubMedGoogle Scholar
  345. 345.
    Wallace JL, Dicay M, McKnight W, Martin GR (2007) Hydrogen sulfide enhances ulcer healing in rats. FASEB J 21(14):4070–4076. CrossRefPubMedGoogle Scholar
  346. 346.
    Mok YY, Moore PK (2008) Hydrogen sulphide is pro-inflammatory in haemorrhagic shock. Inflamm Res 57(11):512–518. CrossRefPubMedGoogle Scholar
  347. 347.
    Mariggio MA, Minunno V, Riccardi S, Santacroce R, De Rinaldis P, Fumarulo R (1998) Sulfide enhancement of PMN apoptosis. Immunopharmacol Immunotoxicol 20(3):399–408. CrossRefPubMedGoogle Scholar
  348. 348.
    Papapetropoulos A, Pyriochou A, Altaany Z, Yang G, Marazioti A, Zhou Z, Jeschke MG, Branski LK, Herndon DN, Wang R, Szabo C (2009) Hydrogen sulfide is an endogenous stimulator of angiogenesis. Proc Natl Acad Sci U S A 106(51):21972–21977. CrossRefPubMedPubMedCentralGoogle Scholar
  349. 349.
    Jang H, Oh MY, Kim YJ, Choi IY, Yang HS, Ryu WS, Lee SH, Yoon BW (2014) Hydrogen sulfide treatment induces angiogenesis after cerebral ischemia. J Neurosci Res 92(11):1520–1528. CrossRefPubMedGoogle Scholar
  350. 350.
    Blackler RW, Gemici B, Manko A, Wallace JL (2014) NSAID-gastroenteropathy: new aspects of pathogenesis and prevention. Curr Opin Pharmacol 19:11–16. CrossRefPubMedGoogle Scholar
  351. 351.
    Motta JP, Flannigan KL, Agbor TA, Beatty JK, Blackler RW, Workentine ML, Da Silva GJ, Wang R, Buret AG, Wallace JL (2015) Hydrogen sulfide protects from colitis and restores intestinal microbiota biofilm and mucus production. Inflamm Bowel Dis 21(5):1006–1017. CrossRefPubMedGoogle Scholar
  352. 352.
    Palinkas Z, Furtmuller PG, Nagy A, Jakopitsch C, Pirker KF, Magierowski M, Jasnos K, Wallace JL, Obinger C, Nagy P (2015) Interactions of hydrogen sulfide with myeloperoxidase. Br J Pharmacol 172(6):1516–1532. CrossRefPubMedGoogle Scholar
  353. 353.
    Nicotera P, Brune B, Bagetta G (1997) Nitric oxide: inducer or suppressor of apoptosis? Trends Pharmacol Sci 18(6):189–190CrossRefPubMedGoogle Scholar
  354. 354.
    Kim YM, Bombeck CA, Billiar TR (1999) Nitric oxide as a bifunctional regulator of apoptosis. Circ Res 84(3):253–256CrossRefPubMedGoogle Scholar
  355. 355.
    Brune B (2005) The intimate relation between nitric oxide and superoxide in apoptosis and cell survival. Antioxid Redox Signal 7(3–4):497–507. CrossRefPubMedGoogle Scholar
  356. 356.
    Guillen MI, Megias J, Clerigues V, Gomar F, Alcaraz MJ (2008) The CO-releasing molecule CORM-2 is a novel regulator of the inflammatory process in osteoarthritic chondrocytes. Rheumatology (Oxford) 47(9):1323–1328. CrossRefGoogle Scholar
  357. 357.
    Megias J, Guillen MI, Bru A, Gomar F, Alcaraz MJ (2008) The carbon monoxide-releasing molecule tricarbonyldichlororuthenium(II) dimer protects human osteoarthritic chondrocytes and cartilage from the catabolic actions of interleukin-1beta. J Pharmacol Exp Ther 325(1):56–61. CrossRefPubMedGoogle Scholar
  358. 358.
    Urquhart P, Rosignoli G, Cooper D, Motterlini R, Perretti M (2007) Carbon monoxide-releasing molecules modulate leukocyte-endothelial interactions under flow. J Pharmacol Exp Ther 321(2):656–662. CrossRefPubMedGoogle Scholar
  359. 359.
    Chiang N, Shinohara M, Dalli J, Mirakaj V, Kibi M, Choi AM, Serhan CN (2013) Inhaled carbon monoxide accelerates resolution of inflammation via unique proresolving mediator-heme oxygenase-1 circuits. J Immunol 190(12):6378–6388. CrossRefPubMedPubMedCentralGoogle Scholar
  360. 360.
    Motterlini R, Foresti R (2014) Heme oxygenase-1 as a target for drug discovery. Antioxid Redox Signal 20(11):1810–1826. CrossRefPubMedGoogle Scholar
  361. 361.
    Moncada S, Palmer RM, Higgs EA (1991) Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43(2):109–142PubMedGoogle Scholar
  362. 362.
    Armstrong R (2001) The physiological role and pharmacological potential of nitric oxide in neutrophil activation. Int Immunopharmacol 1(8):1501–1512CrossRefPubMedGoogle Scholar
  363. 363.
    Ma L, Wallace JL (2000) Endothelial nitric oxide synthase modulates gastric ulcer healing in rats. Am J Physiol Gastrointest Liver Physiol 279(2):G341–G346CrossRefPubMedGoogle Scholar
  364. 364.
    Pilane CM, LaBelle EF (2004) NO induced apoptosis of vascular smooth muscle cells accompanied by ceramide increase. J Cell Physiol 199(2):310–315. CrossRefPubMedGoogle Scholar
  365. 365.
    Ridnour LA, Thomas DD, Switzer C, Flores-Santana W, Isenberg JS, Ambs S, Roberts DD, Wink DA (2008) Molecular mechanisms for discrete nitric oxide levels in cancer. Nitric Oxide Biol Chem 19(2):73–76. CrossRefGoogle Scholar
  366. 366.
    Burke AJ, Sullivan FJ, Giles FJ, Glynn SA (2013) The yin and yang of nitric oxide in cancer progression. Carcinogenesis 34(3):503–512. CrossRefPubMedGoogle Scholar
  367. 367.
    Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405(6785):458–462. CrossRefPubMedGoogle Scholar
  368. 368.
    Bernik TR, Friedman SG, Ochani M, DiRaimo R, Ulloa L, Yang H, Sudan S, Czura CJ, Ivanova SM, Tracey KJ (2002) Pharmacological stimulation of the cholinergic antiinflammatory pathway. J Exp Med 195(6):781–788CrossRefPubMedPubMedCentralGoogle Scholar
  369. 369.
    Guarini S, Altavilla D, Cainazzo MM, Giuliani D, Bigiani A, Marini H, Squadrito G, Minutoli L, Bertolini A, Marini R, Adamo EB, Venuti FS, Squadrito F (2003) Efferent vagal fibre stimulation blunts nuclear factor-kappaB activation and protects against hypovolemic hemorrhagic shock. Circulation 107(8):1189–1194CrossRefPubMedGoogle Scholar
  370. 370.
    van Westerloo DJ, Giebelen IA, Florquin S, Daalhuisen J, Bruno MJ, de Vos AF, Tracey KJ, van der Poll T (2005) The cholinergic anti-inflammatory pathway regulates the host response during septic peritonitis. J Infect Dis 191(12):2138–2148. CrossRefPubMedGoogle Scholar
  371. 371.
    Ghia JE, Blennerhassett P, El-Sharkawy RT, Collins SM (2007) The protective effect of the vagus nerve in a murine model of chronic relapsing colitis. Am J Physiol Gastrointest Liver Physiol 293(4):G711–G718. CrossRefPubMedGoogle Scholar
  372. 372.
    Rosas-Ballina M, Ochani M, Parrish WR, Ochani K, Harris YT, Huston JM, Chavan S, Tracey KJ (2008) Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia. Proc Natl Acad Sci U S A 105(31):11008–11013. CrossRefPubMedPubMedCentralGoogle Scholar
  373. 373.
    Inoue T, Abe C, Sung SS, Moscalu S, Jankowski J, Huang L, Ye H, Rosin DL, Guyenet PG, Okusa MD (2016) Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through alpha7nAChR+ splenocytes. J Clin Invest 126(5):1939–1952. CrossRefPubMedPubMedCentralGoogle Scholar
  374. 374.
    Huston JM, Ochani M, Rosas-Ballina M, Liao H, Ochani K, Pavlov VA, Gallowitsch-Puerta M, Ashok M, Czura CJ, Foxwell B, Tracey KJ, Ulloa L (2006) Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis. J Exp Med 203(7):1623–1628. CrossRefPubMedPubMedCentralGoogle Scholar
  375. 375.
    Mina-Osorio P, Rosas-Ballina M, Valdes-Ferrer SI, Al-Abed Y, Tracey KJ, Diamond B (2012) Neural signaling in the spleen controls B-cell responses to blood-borne antigen. Mol Med 18:618–627. CrossRefPubMedPubMedCentralGoogle Scholar
  376. 376.
    Levine YA, Koopman FA, Faltys M, Caravaca A, Bendele A, Zitnik R, Vervoordeldonk MJ, Tak PP (2014) Neurostimulation of the cholinergic anti-inflammatory pathway ameliorates disease in rat collagen-induced arthritis. PLoS One 9(8):e104530. CrossRefPubMedPubMedCentralGoogle Scholar
  377. 377.
    Leib C, Goser S, Luthje D, Ottl R, Tretter T, Lasitschka F, Zittrich S, Pfitzer G, Katus HA, Kaya Z (2011) Role of the cholinergic antiinflammatory pathway in murine autoimmune myocarditis. Circ Res 109(2):130–140. CrossRefPubMedGoogle Scholar
  378. 378.
    Mao X, Xing H, Mao A, Jiang H, Cheng L, Liu Y, Quan X, Li L (2014) Netrin-1 attenuates cardiac ischemia reperfusion injury and generates alternatively activated macrophages. Inflammation 37(2):573–580. CrossRefPubMedGoogle Scholar
  379. 379.
    Ly NP, Komatsuzaki K, Fraser IP, Tseng AA, Prodhan P, Moore KJ, Kinane TB (2005) Netrin-1 inhibits leukocyte migration in vitro and in vivo. Proc Natl Acad Sci U S A 102(41):14729–14734. CrossRefPubMedPubMedCentralGoogle Scholar
  380. 380.
    Aherne CM, Collins CB, Eltzschig HK (2013) Netrin-1 guides inflammatory cell migration to control mucosal immune responses during intestinal inflammation. Tissue Barriers 1(2):e24957. CrossRefPubMedPubMedCentralGoogle Scholar
  381. 381.
    Schlegel M, Kohler D, Korner A, Granja T, Straub A, Giera M, Mirakaj V (2016) The neuroimmune guidance cue netrin-1 controls resolution programs and promotes liver regeneration. Hepatology 63(5):1689–1705. CrossRefPubMedGoogle Scholar
  382. 382.
    Elajami TK, Colas RA, Dalli J, Chiang N, Serhan CN, Welty FK (2016) Specialized proresolving lipid mediators in patients with coronary artery disease and their potential for clot remodeling. FASEB J 30(8):2792–2801. CrossRefPubMedPubMedCentralGoogle Scholar
  383. 383.
    Mirakaj V, Gatidou D, Potzsch C, Konig K, Rosenberger P (2011) Netrin-1 signaling dampens inflammatory peritonitis. J Immunol 186(1):549–555. CrossRefPubMedGoogle Scholar
  384. 384.
    Serhan CN, Takano T, Gronert K, Chiang N, Clish CB (1999) Lipoxin and aspirin-triggered 15-epi-lipoxin cellular interactions anti-inflammatory lipid mediators. Clin Chem Lab Med 37(3):299–309. CrossRefPubMedGoogle Scholar
  385. 385.
    Pouliot M, Serhan CN (1999) Lipoxin A4 and aspirin-triggered 15-epi-LXA4 inhibit tumor necrosis factor-alpha-initiated neutrophil responses and trafficking: novel regulators of a cytokine-chemokine axis relevant to periodontal diseases. J Periodontal Res 34(7):370–373CrossRefPubMedGoogle Scholar
  386. 386.
    Maddox JF, Serhan CN (1996) Lipoxin A4 and B4 are potent stimuli for human monocyte migration and adhesion: selective inactivation by dehydrogenation and reduction. J Exp Med 183(1):137–146CrossRefPubMedGoogle Scholar
  387. 387.
    Serhan CN, Jain A, Marleau S, Clish C, Kantarci A, Behbehani B, Colgan SP, Stahl GL, Merched A, Petasis NA, Chan L, Van Dyke TE (2003) Reduced inflammation and tissue damage in transgenic rabbits overexpressing 15-Lipoxygenase and endogenous anti-inflammatory lipid mediators. J Immunol 171(12):6856–6865CrossRefPubMedGoogle Scholar
  388. 388.
    Sugimoto MA, Ribeiro ALC, Costa BRC, Vago JP, Lima KM, Carneiro FS, Ortiz MMO, Lima GLN, Carmo AF, Rocha RM, Perez DA, Reis AC, Pinho V, Miles LA, Garcia CC, Teixeira MM, Sousa LP (2017) Plasmin and plasminogen induce macrophage reprogramming and regulate key steps of inflammation resolution via annexin A1. Blood 129(21):2896–2907. CrossRefPubMedPubMedCentralGoogle Scholar
  389. 389.
    Bhardwaj RS, Schwarz A, Becher E, Mahnke K, Aragane Y, Schwarz T, Luger TA (1996) Pro-opiomelanocortin-derived peptides induce IL-10 production in human monocytes. J Immunol 156(7):2517–2521PubMedGoogle Scholar
  390. 390.
    La M, Cao TV, Cerchiaro G, Chilton K, Hirabayashi J, Kasai K, Oliani SM, Chernajovsky Y, Perretti M (2003) A novel biological activity for galectin-1. Am J Pathol 163(4):1505–1515CrossRefPubMedPubMedCentralGoogle Scholar
  391. 391.
    Bizzarro V, Belvedere R, Piaz FD, Parente L, Petrella A, Hotchin NA (2012) Annexin A1 induces skeletal muscle cell migration acting through formyl peptide receptors. PLoS One 7(10):e48246. CrossRefPubMedPubMedCentralGoogle Scholar
  392. 392.
    Campbell EL, Louis NA, Tomassetti SE, Canny GO, Arita M, Serhan CN, Colgan SP (2007) Resolvin E1 promotes mucosal surface clearance of neutrophils: a new paradigm for inflammatory resolution. FASEB J 21(12):3162–3170. CrossRefPubMedGoogle Scholar
  393. 393.
    Haworth O, Cernadas M, Yang R, Serhan CN, Levy BD (2008) Resolvin E1 regulates interleukin 23, interferon-γ and lipoxin A4 to promote the resolution of allergic airway inflammation. Nat Immunol 9(8):873–879. CrossRefPubMedPubMedCentralGoogle Scholar
  394. 394.
    Jin Y, Arita M, Zhang Q, Saban DR, Chauhan SK, Chiang N, Serhan CN, Dana R (2009) Anti-angiogenesis effect of the novel antiinflammatory and pro-resolving lipid mediators. Invest Ophthalmol Vis Sci 50(10):4743–4752. CrossRefPubMedPubMedCentralGoogle Scholar
  395. 395.
    Dalli J, Winkler JW, Colas RA, Arnardottir H, Cheng CYC, Chiang N, Petasis NA, Serhan CN (2013) Resolvin D3 and aspirin-triggered resolvin D3 are potent immunoresolvents. Chem Biol 20(2):188–201. CrossRefPubMedPubMedCentralGoogle Scholar
  396. 396.
    Kebir DE, Gjorstrup P, Filep JG (2012) Resolvin E1 promotes phagocytosis-induced neutrophil apoptosis and accelerates resolution of pulmonary inflammation. Proc Natl Acad Sci U S A 109(37):14983–14988. CrossRefPubMedPubMedCentralGoogle Scholar
  397. 397.
    Pope NH, Salmon M, Davis JP, Chatterjee A, Su G, Conte MS, Ailawadi G, Upchurch GR (2016) D-series resolvins inhibit murine abdominal aortic aneurysm formation and increase M2 macrophage polarization. FASEB J 30(12):4192–4201. CrossRefPubMedPubMedCentralGoogle Scholar
  398. 398.
    Bazan NG, Eady TN, Khoutorova L, Atkins KD, Hong S, Lu Y, Zhang C, Jun B, Obenaus A, Fredman G, Zhu M, Winkler JW, Petasis NA, Serhan CN, Belayev L (2012) Novel aspirin-triggered neuroprotectin D1 attenuates cerebral ischemic injury after experimental stroke. Exp Neurol 236(1):122–130. CrossRefPubMedPubMedCentralGoogle Scholar
  399. 399.
    Mukherjee PK, Chawla A, Loayza MS, Bazan NG (2007) Docosanoids are multifunctional regulators of neural cell integrity and fate: significance in aging and disease. Prostaglandins Leukot Essent Fat Acids 77(5–6):233–238. CrossRefGoogle Scholar
  400. 400.
    Mukherjee PK, Marcheselli VL, Barreiro S, Hu J, Bok D, Bazan NG (2007) Neurotrophins enhance retinal pigment epithelial cell survival through neuroprotectin D1 signaling. Proc Natl Acad Sci U S A 104(32):13152–13157. CrossRefPubMedPubMedCentralGoogle Scholar
  401. 401.
    Serhan CN, Yang R, Martinod K, Kasuga K, Pillai PS, Porter TF, Oh SF, Spite M (2009) Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions. J Exp Med 206(1):15–23. CrossRefPubMedPubMedCentralGoogle Scholar
  402. 402.
    Edenius C, Haeggström J, Lindgren JA (1988) Transcellular conversion of endogenous arachidonic acid to lipoxins in mixed human plateletgranulocyte suspensions. Biochem Biophys Res Commun 157(2):801–807CrossRefPubMedGoogle Scholar
  403. 403.
    Perretti M, Leroy X, Bland EJ, Montero-Melendez T (2015) Resolution pharmacology: opportunities for therapeutic innovation in inflammation. Trends Pharmacol Sci 36(11):737–755. CrossRefPubMedGoogle Scholar
  404. 404.
    Serhan CN (2005) Lipoxins and aspirin-triggered 15-epi-lipoxins are the first lipid mediators of endogenous anti-inflammation and resolution. Prostaglandins Leukot Essent Fat Acids 73(3–4):141–162. CrossRefGoogle Scholar
  405. 405.
    Serhan CN (2007) Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu Rev Immunol 25(1):101–137. CrossRefPubMedGoogle Scholar
  406. 406.
    Isobe Y, Arita M, Iwamoto R, Urabe D, Todoroki H, Masuda K, Inoue M, Arai H (2013) Stereochemical assignment and anti-inflammatory properties of the omega-3 lipid mediator resolvin E3. J Biochem 153(4):355–360. CrossRefPubMedGoogle Scholar
  407. 407.
    Capdevila JH, Wei S, Helvig C, Falck JR, Belosludtsev Y, Truan G, Graham-Lorence SE, Peterson JA (1996) The highly stereoselective oxidation of polyunsaturated fatty acids by cytochrome P450BM-3. J Biol Chem 271:22663–22671CrossRefPubMedGoogle Scholar
  408. 408.
    Serhan CN, Fredman G, Yang R, Karamnov S, Belayev LS, Bazan NG, Zhu M, Winkler JW, Petasis NA (2011) Novel proresolving aspirin-triggered DHA pathway. Chem Biol 18(8):976–987. CrossRefPubMedPubMedCentralGoogle Scholar
  409. 409.
    Serhan CN, Yang R, Martinod K, Kasuga K, Pillai PS, Porter TF, Oh SF, Spite M (2009) Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions. J Exp Med 206(1):15–23. CrossRefPubMedPubMedCentralGoogle Scholar
  410. 410.
    Dalli J, Zhu M, Vlasenko NA, Deng B, Haeggström JZ, Petasis NA, Serhan CN (2013) The novel 13,14 -epoxy-maresin is converted by human macrophages to maresin 1 (MaR1), inhibits leukotriene A hydrolase (LTA H), and shifts macrophage phenotype. FASEB J 27(7):2573–2583. CrossRefPubMedPubMedCentralGoogle Scholar
  411. 411.
    Dalli J, Chiang N, Serhan CN (2014) Identification of 14-series sulfido-conjugated mediators that promote resolution of infection and organ protection. Proc Natl Acad Sci U S A 111(44):E4753–E4761. CrossRefPubMedPubMedCentralGoogle Scholar
  412. 412.
    Gobbetti T, Cooray SN (2016) Annexin A1 and resolution of inflammation: tissue repairing properties and signalling signature. Biol Chem 397(10):981–993. CrossRefPubMedGoogle Scholar
  413. 413.
    Li Y, Cai L, Wang H, Wu P, Gu W, Chen Y, Hao H, Tang K, Yi P, Liu M, Miao S, Ye D (2011) Pleiotropic regulation of macrophage polarization and tumorigenesis by formyl peptide receptor-2. Oncogene 30(36):3887–3899. CrossRefPubMedGoogle Scholar
  414. 414.
    Luger TA, Kalden DH, Scholzen TE, Brzoska T (2000) Alpha-melanocyte-stimulating hormone as a mediator of tolerance induction. Pathobiology 67(5-6):318–321. CrossRefGoogle Scholar
  415. 415.
    Chan LF, Metherell LA, Clark AJL (2011) Effects of melanocortins on adrenal gland physiology. Eur J Pharmacol 660(1):171–180. CrossRefPubMedGoogle Scholar
  416. 416.
    Magenis RE, Smith L, Nadeau JH, Johnson KR, Mountjoy KG, Cone RD (1994) Mapping of the ACTH, MSH, and neural (MC3 and MC4) melanocortin receptors in the mouse and human. Mamm Genome 5:503–508CrossRefPubMedGoogle Scholar
  417. 417.
    Mountjoy KG, Mortrud MT, Low MJ, Simerly RB, Cone RD (1994) Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol Endocrinol 8(10):1298–1308PubMedGoogle Scholar
  418. 418.
    Patel HB, Montero-Melendez T, Greco KV, Perretti M (2011) Melanocortin receptors as novel effectors of macrophage responses in inflammation. Front Immunol 2:41. CrossRefPubMedPubMedCentralGoogle Scholar
  419. 419.
    Cummings RD, Liu FT (2009) Galectins. In: Varki A, Cummings RD, Esko JD et al (eds) Essentials of glycobiology, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor. Chapter 33. Available from: Google Scholar
  420. 420.
    Cooper D, Norling LV, Perretti M (2008) Novel insights into the inhibitory effects of Galectin-1 on neutrophil recruitment under flow. J Leukoc Biol 83(6):1459–1466. CrossRefPubMedGoogle Scholar
  421. 421.
    Brancaleone V, Mitidieri E, Flower RJ, Cirino G, Perretti M (2014) Annexin A1 mediates hydrogen sulfide properties in the control of inflammation. J Pharmacol Exp Ther 351(1):96–104. CrossRefPubMedPubMedCentralGoogle Scholar
  422. 422.
    Wang Y, Jia J, Ao G, Hu L, Liu H, Xiao Y, Du H, Alkayed NJ, Liu CF, Cheng J (2014) Hydrogen sulfide protects blood-brain barrier integrity following cerebral ischemia. J Neurochem 129(5):827–838. CrossRefPubMedGoogle Scholar
  423. 423.
    Kimura H (2011) Hydrogen sulfide: its production and functions. Exp Physiol 96(9):833–835. CrossRefPubMedGoogle Scholar
  424. 424.
    Cekic C, Linden J (2016) Purinergic regulation of the immune system. Nat Rev Immunol 16(3):177–192. CrossRefPubMedGoogle Scholar
  425. 425.
    Dickenson JM, Reeder S, Rees B, Alexander S, Kendall D (2003) Functional expression of adenosine A2A and A3 receptors in the mouse dendritic cell line XS-106. Eur J Pharmacol 474(1):43–51CrossRefPubMedGoogle Scholar
  426. 426.
    Gallowitsch-Puerta M, Pavlov VA (2007) Neuro-immune interactions via the cholinergic anti-inflammatory pathway. Life Sci 80(24–25):2325–2329. CrossRefPubMedPubMedCentralGoogle Scholar
  427. 427.
    Ly NP, Komatsuzaki K, Fraser IP, Tseng AA, Prodhan P, Moore KJ, Kinane TB (2005) Netrin-1 inhibits leukocyte migration in vitro and in vivo. Proc Natl Acad Sci U S A 102(41):14729–14734. CrossRefPubMedPubMedCentralGoogle Scholar
  428. 428.
    Lee CT, Teles R, Kantarci A, Chen T, McCafferty J, Starr JR, Brito LC, Paster BJ, Van Dyke TE (2016) Resolvin E1 reverses experimental periodontitis and dysbiosis. J Immunol 197(7):2796–2806. CrossRefPubMedPubMedCentralGoogle Scholar
  429. 429.
    Wang H, Anthony D, Yatmaz S, Wijburg O, Satzke C, Levy B, Vlahos R, Bozinovski S (2017) Aspirin-triggered resolvin D1 reduces pneumococcal lung infection and inflammation in a viral and bacterial coinfection pneumonia model. Clin Sci (Lond) 131(18):2347–2362. CrossRefGoogle Scholar
  430. 430.
    Rajasagi NK, Reddy PB, Mulik S, Gjorstrup P, Rouse BT (2013) Neuroprotectin D1 reduces the severity of herpes simplex virus-induced corneal immunopathology. Invest Ophthalmol Vis Sci 54(9):6269–6279. CrossRefPubMedPubMedCentralGoogle Scholar
  431. 431.
    Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li JH, Wang H, Yang H, Ulloa L, Al-Abed Y, Czura CJ, Tracey KJ (2003) Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421(6921):384–388. CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • William Antonio Gonçalves
    • 1
  • Alesandra Côrte Reis Melão
    • 1
  • Mauro Martins Teixeira
    • 2
  • Barbara Maximino Rezende
    • 3
    Email author
  • Vanessa Pinho
    • 1
    Email author
  1. 1.Departamento de MorfologiaInstituto de Ciências Biológicas. Universidade Federal de Minas GeraisBelo HorizonteBrazil
  2. 2.Departamento de Bioquímica e ImunologiaInstituto de Ciências Biológicas. Universidade Federal de Minas GeraisBelo HorizonteBrazil
  3. 3.Departamento de Enfermagem BásicaEscola de Enfermagem. Universidade Federal de Minas GeraisBelo HorizonteBrazil

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