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Lipoxins: update and impact of endogenous pro-resolution lipid mediators

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Reviews of Physiology Biochemistry and Pharmacology

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 160))

Abstract

Lipoxins (LXs) are endogenously produced eicosanoids that are typically generated by transcellular biosynthesis. These trihydroxytetraene-containing lipid mediators and their stable synthetic analogues possess a wide spectrum of anti-inflammatory and pro-resolution bioactions both in vitro and in vivo. More recently, LXs have emerged as potential anti-fibrotic mediators that may influence pro-fibrotic cytokines and matrix-associated gene expression in response to platelet-derived growth factor (PDGF). Here we review the biosynthesis, metabolism and bioactions of LXs and LX analogues and their therapeutic potential.

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References

  • Abboud HE (1995) Role of platelet-derived growth factor in renal injury. Annu Rev Physiol 57:297–309

    PubMed  CAS  Google Scholar 

  • Aliberti J (2005) Host persistence: exploitation of anti-inflammatory pathways by Toxoplasma gondii. Nat Rev Immunol 5:162–170

    PubMed  CAS  Google Scholar 

  • Aliberti J, Serhan C, Sher A (2002) Parasite-induced lipoxin A4 is an endogenous regulator of IL-12 production and immunopathology in Toxoplasma gondii infection. J Exp Med 196:1253–1262

    PubMed  CAS  Google Scholar 

  • Arita M, Oh SF, Chonan T, Hong S, Elangovan S, Sun YP, Uddin J, Petasis NA, Serhan CN (2006) Metabolic inactivation of resolvin E1 and stabilization of its anti-inflammatory actions. J Biol Chem 281:22847–22854

    PubMed  CAS  Google Scholar 

  • Badr KF, DeBoer DK, Schwartzberg M, Serhan CN (1989) Lipoxin A4 antagonizes cellular and in vivo actions of leukotriene D4 in rat glomerular mesangial cells: evidence for competition at a common receptor. Proc Natl Acad Sci USA 86:3438–3442

    PubMed  CAS  Google Scholar 

  • Bafica A, Scanga CA, Serhan C, Machado F, White S, Sher A, Aliberti J (2005) Host control of Mycobacterium tuberculosis is regulated by 5-lipoxygenase-dependent lipoxin production. J Clin Invest 115:1601–1606

    PubMed  CAS  Google Scholar 

  • Bannenberg GL, Aliberti J, Hong S, Sher A, Serhan C (2004) Exogenous pathogen and plant 15-lipoxygenase initiate endogenous lipoxin A4 biosynthesis. J Exp Med 199:515–523

    PubMed  CAS  Google Scholar 

  • Bazan HE (2005) Cellular and molecular events in corneal wound healing: significance of lipid signalling. Exp Eye Res 80:453–463

    PubMed  CAS  Google Scholar 

  • Bonnans C, Chanez P, Chavis C (2004) Lipoxins in asthma: potential therapeutic mediators on bronchial inflammation? Allergy 59:1027–1041

    PubMed  CAS  Google Scholar 

  • Bonnans C, Fukunaga K, Levy MA, Levy BD (2006) Lipoxin A(4) regulates bronchial epithelial cell responses to acid injury. Am J Pathol 168:1064–1072

    PubMed  CAS  Google Scholar 

  • Brady HR, Persson U, Ballermann BJ, Brenner BM, Serhan CN (1990) Leukotrienes stimulate neutrophil adhesion to mesangial cells: modulation with lipoxins. Am J Physiol 259:F809–815

    PubMed  CAS  Google Scholar 

  • Brezinski ME, Serhan CN (1990) Selective incorporation of (15S)-hydroxyeicosatetraenoic acid in phosphatidylinositol of human neutrophils: agonist-induced deacylation and transformation of stored hydroxyeicosanoids. Proc Natl Acad Sci USA 87:6248–6252

    PubMed  CAS  Google Scholar 

  • Cezar-de-Mello PF, Nascimento-Silva V, Villela CG, Fierro IM (2006) Aspirin-triggered Lipoxin A4 inhibition of VEGF-induced endothelial cell migration involves actin polymerization and focal adhesion assembly. Oncogene 25:122–129

    PubMed  CAS  Google Scholar 

  • Chiang N, Fierro IM, Gronert K, Serhan CN (2000) Activation of lipoxin A(4) receptors by aspirin-triggered lipoxins and select peptides evokes ligand-specific responses in inflammation. J Exp Med 191:1197–1208

    PubMed  CAS  Google Scholar 

  • Chiang N, Takano T, Arita M, Watanabe S, Serhan CN (2003) A novel rat lipoxin A4 receptor that is conserved in structure and function. Br J Pharmacol 139:89–98

    PubMed  CAS  Google Scholar 

  • Chiang N, Hurwitz S, Ridker PM, Serhan CN (2006) Aspirin has a gender-dependent impact on antiinflammatory 15-epi-lipoxin A4 formation: a randomized human trial. Arterioscler Thromb Vasc Biol 26:e14–17

    PubMed  CAS  Google Scholar 

  • Claria J, Serhan CN (1995) Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. Proc Natl Acad Sci USA 92:9475–9479

    PubMed  CAS  Google Scholar 

  • Clish CB, O'Brien JA, Gronert K, Stahl GL, Petasis NA, Serhan CN (1999) Local and systemic delivery of a stable aspirin-triggered lipoxin prevents neutrophil recruitment in vivo. Proc Natl Acad Sci USA 96:8247–8252

    PubMed  CAS  Google Scholar 

  • Clish CB, Levy BD, Chiang N, Tai HH, Serhan CN (2000) Oxidoreductases in lipoxin A4 metabolic inactivation: a novel role for 15-onoprostaglandin 13-reductase/leukotriene B4 12-hydroxydehydrogenase in inflammation. J Biol Chem 275:25372–25380

    PubMed  CAS  Google Scholar 

  • Colgan SP, Serhan CN, Parkos CA, Delp-Archer C, Madara JL (1993) Lipoxin A4 modulates transmigration of human neutrophils across intestinal epithelial monolayers. J Clin Invest 92:75–82

    PubMed  CAS  Google Scholar 

  • Cybulsky AV (2000) Growth factor pathways in proliferative glomerulonephritis. Curr Opin Nephrol Hypertens 9:217–223

    PubMed  CAS  Google Scholar 

  • Devchand PR, Schmidt BA, Primo VC, Zhang QY, Arnaout MA, Serhan CN, Nikolic B (2005) A synthetic eicosanoid LX-mimetic unravels host-donor interactions in allogeneic BMT-induced GvHD to reveal an early protective role for host neutrophils. FASEB J 19:203–210

    PubMed  CAS  Google Scholar 

  • Edenius C, Haeggstrom J, Lindgren JA (1988) Transcellular conversion of endogenous arachidonic acid to lipoxins in mixed human platelet-granulocyte suspensions. Biochem Biophys Res Commun 157:801–807

    PubMed  CAS  Google Scholar 

  • Elson CO, Sartor RB, Tennyson GS, Riddell RH (1995) Experimental models of inflammatory bowel disease. Gastroenterology 109:1344–1367

    PubMed  CAS  Google Scholar 

  • Fierro IM (2005) Angiogenesis and lipoxins. Prostaglandins Leukot Essent Fatty Acids 73:271–275

    PubMed  CAS  Google Scholar 

  • Fierro IM, Kutok JL, Serhan CN (2002) Novel lipid mediator regulators of endothelial cell proliferation and migration: aspirin-triggered-15R-lipoxin A(4) and lipoxin A(4). J Pharmacol Exp Ther 300:385–392

    PubMed  CAS  Google Scholar 

  • Fierro IM, Colgan SP, Bernasconi G, Petasis NA, Clish CB, Arita M, Serhan CN (2003) Lipoxin A4 and aspirin-triggered 15-epi-lipoxin A4 inhibit human neutrophil migration: comparisons between synthetic 15 epimers in chemotaxis and transmigration with microvessel endothelial cells and epithelial cells. J Immunol 170:2688–2694

    PubMed  CAS  Google Scholar 

  • Filep JG, Khreiss T, Jozsef L (2005) Lipoxins and aspirin-triggered lipoxins in neutrophil adhesion and signal transduction. Prostaglandins Leukot Essent Fatty Acids 73:257–262

    PubMed  CAS  Google Scholar 

  • Fiore S, Ryeom SW, Weller PF, Serhan CN (1992) Lipoxin recognition sites. Specific binding of labeled lipoxin A4 with human neutrophils. J Biol Chem 267:16168–16176

    PubMed  CAS  Google Scholar 

  • 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 172:1451–1457

    PubMed  CAS  Google Scholar 

  • Fiore S, Serhan CN (1995) Lipoxin A4 receptor activation is distinct from that of the formyl peptide receptor in myeloid cells: inhibition of CD11/18 expression by lipoxin A4-lipoxin A4 receptor interaction. Biochemistry 34:16678–16686

    PubMed  CAS  Google Scholar 

  • 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 180:253–260

    PubMed  CAS  Google Scholar 

  • Fiorucci S, de Lima OM Jr, Mencarelli A, Palazzetti B, Distrutti E, McKnight W, Dicay M, Ma L, Romano M, Morelli A, Wallace JL (2002) Cyclooxygenase-2-derived lipoxin A4 increases gastric resistance to aspirin-induced damage. Gastroenterology 123:1598–1606

    PubMed  CAS  Google Scholar 

  • Fiorucci S, Santucci L, Wallace JL, Sardina M, Romano M, del Soldato P, Morelli A (2003) Interaction of a selective cyclooxygenase-2 inhibitor with aspirin and NO-releasing aspirin in the human gastric mucosa. Proc Natl Acad Sci USA 100:10937–10941

    PubMed  CAS  Google Scholar 

  • Fiorucci S, Wallace JL, Mencarelli A, Distrutti E, Rizzo G, Farneti S, Morelli A, Tseng JL, Suramanyam B, Guilford WJ, Parkinson JF (2004) A beta-oxidation-resistant lipoxin A4 analog treats hapten-induced colitis by attenuating inflammation and immune dysfunction. Proc Natl Acad Sci USA 101:15736–15741

    PubMed  CAS  Google Scholar 

  • Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1:27–31

    PubMed  CAS  Google Scholar 

  • Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 267:10931–10934

    PubMed  CAS  Google Scholar 

  • Gangemi S, Pescara L, D'Urbano E, Basile G, Nicita-Mauro V, Davi G, Romano M (2005) Aging is characterized by a profound reduction in anti-inflammatory lipoxin A4 levels. Exp Gerontol 40:612–614

    PubMed  CAS  Google Scholar 

  • Gewirtz AT, Collier-Hyams LS, Young AN, Kucharzik T, Guilford WJ, Parkinson JF, Williams IR, Neish AS, Madara JL (2002) Lipoxin a4 analogs attenuate induction of intestinal epithelial proinflammatory gene expression and reduce the severity of dextran sodium sulfate-induced colitis. J Immunol 168:5260–5267

    PubMed  CAS  Google Scholar 

  • Gilbert RE, Kelly DJ, McKay T, Chadban S, Hill PA, Cooper ME, Atkins RC, Nikolic-Paterson DJ (2001) PDGF signal transduction inhibition ameliorates experimental mesangial proliferative glomerulonephritis. Kidney Int 59:1324–1332

    PubMed  CAS  Google Scholar 

  • 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 164:1663–1667

    PubMed  CAS  Google Scholar 

  • Goetzl EJ, An S, Smith WL (1995) Specificity of expression and effects of eicosanoid mediators in normal physiology and human diseases. FASEB J 9:1051–1058

    PubMed  CAS  Google Scholar 

  • Goh J, Baird AW, O'Keane C, Watson RW, Cottell D, Bernasconi G, Petasis NA, Godson C, Brady HR, MacMathuna P (2001) Lipoxin A(4) and aspirin-triggered 15-epi-lipoxin A(4) antagonize TNF-alpha-stimulated neutrophil-enterocyte interactions in vitro and attenuate TNF-alpha-induced chemokine release and colonocyte apoptosis in human intestinal mucosa ex vivo. J Immunol 167:2772–2780

    PubMed  CAS  Google Scholar 

  • Gronert K, Gewirtz A, Madara JL, Serhan CN (1998) Identification of a human enterocyte lipoxin A4 receptor that is regulated by interleukin (IL)-13 and interferon gamma and inhibits tumor necrosis factor alpha-induced IL-8 release. J Exp Med 187:1285–1294

    PubMed  CAS  Google Scholar 

  • Gronert K, Martinsson-Niskanen T, Ravasi S, Chiang N, Serhan CN (2001) Selectivity of recombinant human leukotriene D(4), leukotriene B(4), and lipoxin A(4) receptors with aspirin-triggered 15-epi-LXA(4) and regulation of vascular and inflammatory responses. Am J Pathol 158:3–9

    PubMed  CAS  Google Scholar 

  • Gronert K, Maheshwari N, Khan N, Hassan IR, Dunn M, Laniado Schwartzman M (2005) A role for the mouse 12/15-lipoxygenase pathway in promoting epithelial wound healing and host defense. J Biol Chem 280:15267–15278

    PubMed  CAS  Google Scholar 

  • Gupta AG, Hirakata A, Proia AD (1993) Effect of inhibitors of arachidonic acid metabolism on corneal reepithelialization in the rat. Exp Eye Res 56:701–708

    PubMed  CAS  Google Scholar 

  • 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 278:14677–14687

    PubMed  CAS  Google Scholar 

  • Jozsef L, Zouki C, Petasis NA, Serhan CN, Filep JG (2002) Lipoxin A4 and aspirin-triggered 15-epi-lipoxin A4 inhibit peroxynitrite formation, NF-kappa B and AP-1 activation, and IL-8 gene expression in human leukocytes. Proc Natl Acad Sci USA 99:13266–13271

    PubMed  CAS  Google Scholar 

  • Kantarci A, Van Dyke TE (2003) Lipoxins in chronic inflammation. Crit Rev Oral Biol Med 14:4–12

    PubMed  Google Scholar 

  • Karp CL, Cooper AM (2005) An oily, sustained counter-regulatory response to TB. J Clin Invest 115:1473–1476

    PubMed  CAS  Google Scholar 

  • Kelly DJ, Gilbert RE, Cox AJ, Soulis T, Jerums G, Cooper ME (2001) Aminoguanidine ameliorates overexpression of prosclerotic growth factors and collagen deposition in experimental diabetic nephropathy. J Am Soc Nephrol 12:2098–2107

    PubMed  CAS  Google Scholar 

  • Kieran NE, Doran PP, Connolly SB, Greenan MC, Higgins DF, Leonard M, Godson C, Taylor CT, Henger A, Kretzler M, Burne MJ, Rabb H, Brady HR (2003) Modification of the transcriptomic response to renal ischemia/reperfusion injury by lipoxin analog. Kidney Int 64:480–492

    PubMed  CAS  Google Scholar 

  • Kim SJ (1988) Formation of lipoxins by alveolar macrophages. Biochem Biophys Res Commun 150:870–876

    PubMed  CAS  Google Scholar 

  • Langham RG, Kelly DJ, Maguire J, Dowling JP, Gilbert RE, Thomson NM (2003) Over-expression of platelet-derived growth factor in human diabetic nephropathy. Nephrol Dial Transplant 18:1392–1396

    PubMed  CAS  Google Scholar 

  • Lassila M, Jandeleit-Dahm K, Seah KK, Smith CM, Calkin AC, Allen TJ, Cooper ME (2005) Imatinib attenuates diabetic nephropathy in apolipoprotein E-knockout mice. J Am Soc Nephrol 16:363–373

    PubMed  CAS  Google Scholar 

  • Lee TH, Horton CE, Kyan-Aung U, Haskard D, Crea AE, Spur BW (1989) Lipoxin A4 and lipoxin B4 inhibit chemotactic responses of human neutrophils stimulated by leukotriene B4 and N-formyl-L-methionyl-L-leucyl-L-phenylalanine. Clin Sci (Lond) 77:195–203

    CAS  Google Scholar 

  • Lee TH, Lympany P, Crea AE, Spur BW (1991) Inhibition of leukotriene B4-induced neutrophil migration by lipoxin A4: structure-function relationships. Biochem Biophys Res Commun 180:1416–1421

    PubMed  CAS  Google Scholar 

  • Leonard MO, Hannan K, Burne MJ, Lappin DW, Doran P, Coleman P, Stenson C, Taylor CT, Daniels F, Godson C, Petasis NA, Rabb H, Brady HR (2002) 15-Epi-16-(para-fluorophenoxy)-lipoxin A(4)-methyl ester, a synthetic analogue of 15-epi-lipoxin A(4), is protective in experimental ischemic acute renal failure. J Am Soc Nephrol 13:1657–1662

    PubMed  CAS  Google Scholar 

  • Levy BD, Clish CB, Schmidt B, Gronert K, Serhan CN (2001) Lipid mediator class switching during acute inflammation: signals in resolution. Nat Immunol 2:612–619

    PubMed  CAS  Google Scholar 

  • Levy BD, De Sanctis GT, Devchand PR, Kim E, Ackerman K, Schmidt BA, Szczeklik W, Drazen JM, Serhan CN (2002) Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A(4). Nat Med 8:1018–1023

    PubMed  CAS  Google Scholar 

  • Levy BD, Bonnans C, Silverman ES, Palmer LJ, Marigowda G, Israel E (2005) Diminished lipoxin biosynthesis in severe asthma. Am J Respir Crit Care Med 172:824–830

    PubMed  Google Scholar 

  • 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 183:137–146

    PubMed  CAS  Google Scholar 

  • 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 272:6972–6978

    PubMed  CAS  Google Scholar 

  • 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 12:487–494

    PubMed  CAS  Google Scholar 

  • Maderna P, Godson C (2005) Taking insult from injury: lipoxins and lipoxin receptor agonists and phagocytosis of apoptotic cells. Prostaglandins Leukot Essent Fatty Acids 73:179–187

    PubMed  CAS  Google Scholar 

  • Maderna P, Godson C, Hannify G, Murphy M, Brady HR (2000) Influence of lipoxin A(4) and other lipoxygenase-derived eicosanoids on tissue factor expression. Am J Physiol Cell Physiol 279:C945–953

    PubMed  CAS  Google Scholar 

  • Maderna P, Cottell DC, Berlasconi G, Petasis NA, Brady HR, Godson C (2002) Lipoxins induce actin reorganization in monocytes and macrophages but not in neutrophils: differential involvement of rho GTPases. Am J Pathol 160:2275–2283

    PubMed  CAS  Google Scholar 

  • 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 174:3727–3733

    PubMed  CAS  Google Scholar 

  • Marinissen MJ, Gutkind JS (2001) G-protein-coupled receptors and signaling networks: emerging paradigms. Trends Pharmacol Sci 22:368–376

    PubMed  CAS  Google Scholar 

  • Mayadas TN, Mendrick DL, Brady HR, Tang T, Papayianni A, Assmann KJ, Wagner DD, Hynes RO, Cotran RS (1996) Acute passive anti-glomerular basement membrane nephritis in P-selectin-deficient mice. Kidney Int 49:1342–1349

    PubMed  CAS  Google Scholar 

  • McMahon B, Godson C (2004) Lipoxins: endogenous regulators of inflammation. Am J Physiol Renal Physiol 286:F189–201

    PubMed  CAS  Google Scholar 

  • McMahon B, Stenson C, McPhillips F, Fanning A, Brady HR, Godson C (2000) Lipoxin A4 antagonizes the mitogenic effects of leukotriene D4 in human renal mesangial cells. Differential activation of MAP kinases through distinct receptors. J Biol Chem 275:27566–27575

    PubMed  CAS  Google Scholar 

  • McMahon B, Mitchell S, Brady HR, Godson C (2001) Lipoxins: revelations on resolution. Trends Pharmacol Sci 22:391–395

    PubMed  CAS  Google Scholar 

  • McMahon B, Mitchell D, Shattock R, Martin F, Brady HR, Godson C (2002) Lipoxin, leukotriene, and PDGF receptors cross-talk to regulate mesangial cell proliferation. FASEB J 16:1817–1819

    PubMed  CAS  Google Scholar 

  • Mitchell D, Rodgers K, Hanly J, McMahon B, Brady HR, Martin F, Godson C (2004) Lipoxins inhibit Akt/PKB activation and cell cycle progression in human mesangial cells. Am J Pathol 164:937–946

    PubMed  CAS  Google Scholar 

  • Mitchell DM, O'Meara SJ, Gaffney A, Crean JKG, Kinsella BT, Godson C (2006) The Lipoxin A4 receptor is coupled to SHP-2 activation; implications for regulating growth factor receptor signaling. Submitted

    Google Scholar 

  • 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 13:2497–2507

    PubMed  CAS  Google Scholar 

  • Munger KA, Montero A, Fukunaga M, Uda S, Yura T, Imai E, Kaneda Y, Valdivielso JM, Badr KF (1999) Transfection of rat kidney with human 15-lipoxygenase suppresses inflammation and preserves function in experimental glomerulonephritis. Proc Natl Acad Sci USA 96:13375–13380

    PubMed  CAS  Google Scholar 

  • Murakami M, Austen KF, Bingham CO 3rd, Friend DS, Penrose JF, Arm JP (1995) Interleukin-3 regulates development of the 5-lipoxygenase/leukotriene C4 synthase pathway in mouse mast cells. J Biol Chem 270:22653–22656

    PubMed  CAS  Google Scholar 

  • Nakagawa H, Sasahara M, Haneda M, Koya D, Hazama F, Kikkawa R (2000) Immunohistochemical characterization of glomerular PDGF B-chain and PDGF beta-receptor expression in diabetic rats. Diabetes Res Clin Pract 48:87–98

    PubMed  CAS  Google Scholar 

  • Nakamura T, Fukui M, Ebihara I, Osada S, Nagaoka I, Tomino Y, Koide H (1993) mRNA expression of growth factors in glomeruli from diabetic rats. Diabetes 42:450–456

    PubMed  CAS  Google Scholar 

  • Nassar GM, Morrow JD, Roberts LJ 2nd, Lakkis FG, Badr KF (1994) Induction of 15-lipoxygenase by interleukin-13 in human blood monocytes. J Biol Chem 269:27631–27634

    PubMed  CAS  Google Scholar 

  • Ohse T, Ota T, Kieran N, Godson C, Yamada K, Tanaka T, Fujita T, Nangaku M (2004) Modulation of interferon-induced genes by lipoxin analogue in anti-glomerular basement membrane nephritis. J Am Soc Nephrol 15:919–927

    PubMed  CAS  Google Scholar 

  • Papayianni A, Serhan CN, Phillips ML, Rennke HG, Brady HR (1995) Transcellular biosynthesis of lipoxin A4 during adhesion of platelets and neutrophils in experimental immune complex glomerulonephritis. Kidney Int 47:1295–1302

    PubMed  CAS  Google Scholar 

  • Papayianni A, Serhan CN, Brady HR (1996) Lipoxin A4 and B4 inhibit leukotriene-stimulated interactions of human neutrophils and endothelial cells. J Immunol 156:2264–22672

    PubMed  CAS  Google Scholar 

  • Parente L, Perretti M (2003) Advances in the pathophysiology of constitutive and inducible cyclooxygenases: two enzymes in the spotlight. Biochem Pharmacol 65:153–159

    PubMed  CAS  Google Scholar 

  • Perretti M, Chiang N, La M, Fierro IM, Marullo S, Getting SJ, Solito E, Serhan CN (2002) Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor. Nat Med 8:1296–1302

    PubMed  CAS  Google Scholar 

  • Planaguma A, Titos E, Lopez-Parra M, Gaya J, Pueyo G, Arroyo V, Claria J (2002) Aspirin (ASA) regulates 5-lipoxygenase activity and peroxisome proliferator-activated receptor alpha-mediated CINC-1 release in rat liver cells: novel actions of lipoxin A4 (LXA4) and ASA-triggered 15-epi-LXA4. FASEB J 16:1937–1939

    PubMed  CAS  Google Scholar 

  • 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 15:2736–2738

    PubMed  CAS  Google Scholar 

  • 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 176:1878–1888

    PubMed  CAS  Google Scholar 

  • Ring WL, Riddick CA, Baker JR, Munafo DA, Bigby TD (1996) Lymphocytes stimulate expression of 5-lipoxygenase and its activating protein in monocytes in vitro via granulocyte macrophage colony-stimulating factor and interleukin 3. J Clin Invest 97:1293–1301

    PubMed  CAS  Google Scholar 

  • Rodgers K, McMahon B, Mitchell D, Sadlier D, Godson C (2005) Lipoxin A4 modifies platelet-derived growth factor-induced pro-fibrotic gene expression in human renal mesangial cells. Am J Pathol 167:683–694

    PubMed  CAS  Google Scholar 

  • Romano M, Maddox JF, Serhan CN (1996) Activation of human monocytes and the acute monocytic leukemia cell line (THP-1) by lipoxins involves unique signaling pathways for lipoxin A4 versus lipoxin B4: evidence for differential Ca2+ mobilization. J Immunol 157:2149–2154

    PubMed  CAS  Google Scholar 

  • Samuelsson B, Dahlen SE, Lindgren JA, Rouzer CA, Serhan CN (1987) Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science 237:1171–1176

    PubMed  CAS  Google Scholar 

  • Scalia R, Gefen J, Petasis NA, Serhan CN, Lefer AM (1997) Lipoxin A4 stable analogs inhibit leukocyte rolling and adherence in the rat mesenteric microvasculature: role of P-selectin. Proc Natl Acad Sci USA 94:9967–9972

    PubMed  CAS  Google Scholar 

  • Schaldach CM, Riby J, Bjeldanes LF (1999) Lipoxin A4: a new class of ligand for the Ah receptor. Biochemistry 38:7594–7600

    PubMed  CAS  Google Scholar 

  • Serhan CN (2002) Lipoxins and aspirin-triggered 15-epi-lipoxin biosynthesis: an update and role in anti-inflammation and pro-resolution. Prostaglandins Other Lipid Mediat 68–69:433–455

    PubMed  Google Scholar 

  • Serhan CN, Savill J (2005) Resolution of inflammation: the beginning programs the end. Nat Immunol 6:1191–1197

    PubMed  CAS  Google Scholar 

  • 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 85:772–780

    PubMed  CAS  Google Scholar 

  • 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 USA 81:5335–5339

    PubMed  CAS  Google Scholar 

  • Serhan CN, Fiore S, Brezinski DA, Lynch S (1993) Lipoxin A4 metabolism by differentiated HL-60 cells and human monocytes: conversion to novel 15-oxo and dihydro products. Biochemistry 32:6313–6319

    PubMed  CAS  Google Scholar 

  • Serhan CN, Maddox JF, Petasis NA, Akritopoulou-Zanze I, Papayianni A, Brady HR, Colgan SP, Madara JL (1995) Design of lipoxin A4 stable analogs that block transmigration and adhesion of human neutrophils. Biochemistry 34:14609–14615

    PubMed  CAS  Google Scholar 

  • Serhan CN, Haeggstrom JZ, Leslie CC (1996) Lipid mediator networks in cell signaling: update and impact of cytokines. FASEB J 10:1147–1158

    PubMed  CAS  Google Scholar 

  • 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 192:1197–1204

    PubMed  CAS  Google Scholar 

  • 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 196:1025–1037

    PubMed  CAS  Google Scholar 

  • 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 171:6856–6865

    PubMed  CAS  Google Scholar 

  • Simchowitz L, Fiore S, Serhan CN (1994) Carrier-mediated transport of lipoxin A4 in human neutrophils. Am J Physiol 267:C1525–1534

    PubMed  CAS  Google Scholar 

  • 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 164:2660–2666

    PubMed  CAS  Google Scholar 

  • Sodin-Semrl S, Spagnolo A, Barbaro B, Varga J, Fiore S (2004a) Lipoxin A4 counteracts synergistic activation of human fibroblast-like synoviocytes. Int J Immunopathol Pharmacol 17:15–25

    PubMed  CAS  Google Scholar 

  • Sodin-Semrl S, Spagnolo A, Mikus R, Barbaro B, Varga J, Fiore S (2004b) Opposing regulation of interleukin-8 and NF-kappaB responses by lipoxin A4 and serum amyloid A via the common lipoxin A receptor. Int J Immunopathol Pharmacol 17:145–156

    PubMed  CAS  Google Scholar 

  • Souza MH, de Lima OM Jr, Zamuner SR, Fiorucci S, Wallace JL (2003) Gastritis increases resistance to aspirin-induced mucosal injury via COX-2-mediated lipoxin synthesis. Am J Physiol Gastrointest Liver Physiol 285:G54–61

    PubMed  CAS  Google Scholar 

  • Stankova J, Rola-Pleszczynski M, Dubois CM (1995) Granulocyte-macrophage colony-stimulating factor increases 5-lipoxygenase gene transcription and protein expression in human neutrophils. Blood 85:3719–3726

    PubMed  CAS  Google Scholar 

  • Su SB, Gong W, Gao JL, Shen W, Murphy PM, Oppenheim JJ, Wang JM (1999) A seven-transmembrane, G protein-coupled receptor, FPRL1, mediates the chemotactic activity of serum amyloid A for human phagocytic cells. J Exp Med 189:395–402

    PubMed  CAS  Google Scholar 

  • Swirnoff AH, Apel ED, Svaren J, Sevetson BR, Zimonjic DB, Popescu NC, Milbrandt J (1998) Nab1, a corepressor of NGFI-A (Egr-1), contains an active transcriptional repression domain. Mol Cell Biol 18:512–524

    PubMed  CAS  Google Scholar 

  • Takano T, Fiore S, Maddox JF, Brady HR, Petasis NA, Serhan CN (1997) Aspirin-triggered 15-epi-lipoxin A4 (LXA4) and LXA4 stable analogues are potent inhibitors of acute inflammation: evidence for anti-inflammatory receptors. J Exp Med 185:1693–1704

    PubMed  CAS  Google Scholar 

  • Vachier I, Bonnans C, Chavis C, Farce M, Godard P, Bousquet J, Chanez P (2005) Severe asthma is associated with a loss of LX4, an endogenous anti-inflammatory compound. J Allergy Clin Immunol 115:55–60

    PubMed  CAS  Google Scholar 

  • Vaughn MW, Proske RJ, Haviland DL (2002) Identification, cloning, and functional characterization of a murine lipoxin A4 receptor homologue gene. J Immunol 169:3363–3369

    PubMed  CAS  Google Scholar 

  • Wu SH, Lu C, Dong L, Zhou GP, He ZG, Chen ZQ (2005) Lipoxin A inhibits TNF-alpha-induced production of interleukins and proliferation of rat mesangial cells. Kidney Int 68:35–46

    PubMed  CAS  Google Scholar 

  • Wu SH, Wu XH, Lu C, Dong L, Zhou GP, Chen ZQ (2006) Lipoxin A4 inhibits connective tissue growth factor-induced production of chemokines in rat mesangial cells. Kidney Int 69:248–256

    PubMed  CAS  Google Scholar 

  • You M, Flick LM, Yu D, Feng GS (2001) Modulation of the nuclear factor kappa B pathway by Shp-2 tyrosine phosphatase in mediating the induction of interleukin (IL)-6 by IL-1 or tumor necrosis factor. J Exp Med 193:101–110

    PubMed  CAS  Google Scholar 

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Acknowledgements

Work in the authors' laboratory is supported by the Health Research Board, Ireland, Enterprise Ireland, The Welcome Trust, European Commission FP6 funding (LSHM-CT-2004-005033), and The Government of Ireland Programme for Research in Third Level Institutions.

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  1. School of Medicine and Medical Sciences, University College Dublin, UCD Conway Institute of Biomolecular and Biomedical Research and UCB Diabetes Research Center, Belfield, Dublin 4, Ireland

    S. J. O'Meara, K. Rodgers & C. Godson

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  1. S. J. O'Meara
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  2. K. Rodgers
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Correspondence to C. Godson .

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O'Meara, S.J., Rodgers, K., Godson, C. (2007). Lipoxins: update and impact of endogenous pro-resolution lipid mediators. In: Reviews of Physiology Biochemistry and Pharmacology. Reviews of Physiology, Biochemistry and Pharmacology, vol 160. Springer, Berlin, Heidelberg. https://doi.org/10.1007/112_2006_0606

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