Innate Immunity and Inflammation: The Molecular Mechanisms Governing the Cross-Talk Between Innate Immune and Endothelial Cells

  • Daiane Boff
  • Caio Tavares Fagundes
  • Remo Castro Russo
  • Flavio Almeida AmaralEmail author


The innate immune response comprises the initial events that occur during tissue insult, causing cellular activation and triggering inflammation. Innate immune cells, including resident and early migrated cells from the bloodstream, sense a plethora of molecules called molecular patterns, that are derived from microorganisms or host cells. Once activated, pattern recognition receptor (PRR) signalling is triggered intracellularly and promotes the synthesis and release of vasoactive molecules, which target endothelial cells and cause inflammation. In addition, circulating molecules and pathogens also activate PRRs that are expressed on endothelial cells. These events modify endothelial cell metabolism, changing their conformational state and promoting the expression of pro-inflammatory molecules. Importantly, gain-of-function mutations in PRRs are associated with continuous cellular activation, leading to the development of autoinflammatory diseases. Here, we discuss the relationship among the cellular and humoral arms of the innate immune system in inflammatory processes, with special attention given to endothelial cell activation.


Innate immunity Inflammation Pattern recognition receptors Cellular metabolism Autoinflammatory diseases 


Conflicts of Interest

The authors declare no conflicts of interest.


  1. 1.
    Medzhitov R (2008) Origin and physiological roles of inflammation. Nature 454(7203):428–435CrossRefPubMedGoogle Scholar
  2. 2.
    Newton K, Dixit VM (2012) Signaling in innate immunity and inflammation. Cold Spring Harb Perspect Biol 4(3):pii: a006049CrossRefGoogle Scholar
  3. 3.
    Basil MC, Levy BD (2015) Specialized pro-resolving mediators: endogenous regulators of infection and inflammation. Nat Rev Immunol 16(1):51–67. Nature Publishing GroupPubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Bazzoni G, Dejana E (2004) Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev 84(0031–9333 (Print)):869–901PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Cines BDB et al (1998) Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 91(10):3527–3561PubMedPubMedCentralGoogle Scholar
  6. 6.
    Michiels C (2003) Endothelial cell functions. J Cell Physiol 196(3):430–443PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Yau JW, Teoh H, Verma S (2015) Endothelial cell control of thrombosis. BMC Cardiovasc Disord 15:130PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Egan K, FitzGerald GA (2006) Eicosanoids and the vascular endothelium, the vascular endothelium I. Handb Exp Pharmacol 176(Pt 1):189–211CrossRefGoogle Scholar
  9. 9.
    Pober JS, Sessa WC (2007) Evolving functions of endothelial cells in inflammation. Nat Rev Immunol 7(10):803–815PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Komarova YA et al (2017) Protein interactions at endothelial junctions and signaling mechanisms regulating endothelial permeability. Circ Res 120(1):179–206PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Ferraro F et al (2016) Weibel-Palade body size modulates the adhesive activity of its von Willebrand Factor cargo in cultured endothelial cells. Sci Rep 6(August):32473. Nature Publishing GroupPubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Cook-mills JM, Deem TL (2009) Active participation of endothelial cells in inflammation. Pathology 77(4):487–495Google Scholar
  13. 13.
    Mai J et al (2013) An evolving new paradigm: endothelial cells--conditional innate immune cells. J Hematol Oncol 6(1):61PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Fan LM et al (2017) Endothelial cell – specific reactive oxygen species production increases susceptibility to aortic dissection. Circulation 129(25):2661–2672CrossRefGoogle Scholar
  15. 15.
    Muller WA (2014) How endothelial cells regulate transmigration of leukocytes in the inflammatory response. Am J Pathol 184(4):886–896. American Society for Investigative PathologyPubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Takeuchi O, Akira S (2010) Pattern recognition receptors and inflammation. Cell 140(6):805–820. Elsevier IncPubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Vestweber D (2015) How leukocytes cross the vascular endothelium. Nat Rev Immunol 15(11):692–704. Nature Publishing GroupPubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Potente M, Makinen T (2017) Vascular heterogeneity and specialization in development and disease. Nat Rev Mol Cell Biol 18(8):477–494. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights ReservedPubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Ley K, Zarbock A (2017) Hold on to your endothelium: postarrest steps of the leukocyte adhesion cascade. Immunity 25(2):185–187. ElsevierCrossRefGoogle Scholar
  20. 20.
    Zarbock A et al (2011) Leukocyte ligands for endothelial selectins: specialized glycoconjugates that mediate rolling and signaling under flow. Blood 118(26):6743–6751. Washington, DC: American Society of HematologyPubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Zarbock A et al (2008) PSGL-1 engagement by E-selectin signals through Src kinase Fgr and ITAM adapters DAP12 and FcRγ to induce slow leukocyte rolling. J Exp Med 205(10):2339–2347. The Rockefeller University PressPubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Zarbock A, Ley K (2008) Mechanisms and consequences of neutrophil interaction with the endothelium. Am J Pathol 172(1):1–7. American Society for Investigative PathologyPubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Deban L et al (2010) Regulation of leukocyte recruitment by the long pentraxin PTX3. Nat Immunol 11(4):328–334. Nature Publishing GroupPubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Burns AR, Smith CW, Walker DC (2003) Unique structural features that influence neutrophil emigration into the lung. Physiol Rev 83(2):309–336PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Hickey MJ, Westhorpe CLV (2013) Imaging inflammatory leukocyte recruitment in kidney, lung and liver – challenges to the multi-step paradigm. Immunol Cell Biol 91(4):281–289PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Lefrançais E et al (2017) The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature 544(7648):105–109. Macmillan Publishers Limited, part of Springer Nature. All Rights ReservedPubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Yipp BG et al (2017) The lung is a host defense niche for immediate neutrophil-mediated vascular protection. Sci Immunol 2(10):eaam8929PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Kubo H et al (1999) L- and P-selectin and CD11/CD18 in intracapillary neutrophil sequestration in rabbit lungs. Am J Respir Crit Care Med 159(1):267–274. American Thoracic Society – AJRCCMPubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Schilter HC et al (2015) Effects of an anti-inflammatory VAP-1/SSAO inhibitor, PXS-4728A, on pulmonary neutrophil migration. Respir Res 16(1):42. London: BioMed CentralPubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Liu L, Kubes P (2003) Molecular mechanisms of leukocyte recruitment: organ-specific mechanisms of action. Thromb Haemostasis 89(2):213–220. Schattauer PublishersCrossRefGoogle Scholar
  31. 31.
    McDonald B et al (2010) Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science 330(6002):362–366PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Amaral SS et al (2013) Altered responsiveness to extracellular ATP enhances acetaminophen hepatotoxicity. Cell Commun Signal 11:10. BioMed CentralPubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Marques PE et al (2012) Chemokines and mitochondrial products activate neutrophils to amplify organ injury during mouse acute liver failure. Hepatology 56(5):1971–1982PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Haraldsson B, Nyström J, Deen WM (2008) Properties of the glomerular barrier and mechanisms of proteinuria. Physiol Rev 88(2):451–487PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Kuligowski MP, Kitching AR, Hickey MJ (2006) Leukocyte recruitment to the inflamed glomerulus: a critical role for platelet-derived P-selectin in the absence of rolling. J Immunol 176(11):6991–6999PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Janssen ULF, Assmann JM (1998) Improved survival and amelioration in intercellular adhesion molecule- of nephrotoxic 1 knockout mice nephritis. J Am Soc Nephrol 9:1805–1814PubMedPubMedCentralGoogle Scholar
  37. 37.
    Nagao T et al (2007) Up-regulation of adhesion molecule expression in glomerular endothelial cells by anti-myeloperoxidase antibody. Nephrol Dial Transplant 22(1):77–87PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    De Vriese AS et al (1999) The role of selectins in glomerular leukocyte recruitment in rat anti-glomerular basement membrane glomerulonephritis. J Am Soc Nephrol 10(12):2510–2517PubMedPubMedCentralGoogle Scholar
  39. 39.
    Jain A, Pasare C (2017) Innate control of adaptive immunity: beyond the three-signal paradigm. J Immunol 198(10):3791–3800PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Janeway CA (2013) Pillars article: approaching the asymptote? Evolution and revolution in immunology. J Immunol 191(9):4475–4487. Cold Spring Harb Symp Quant Biol 54:1–13, 1989PubMedPubMedCentralGoogle Scholar
  41. 41.
    Grote K, Schütt H, Schieffer B (2011) Toll-like receptors in angiogenesis. Sci World J 11:981–991CrossRefGoogle Scholar
  42. 42.
    Liu J, Cao X (2016) Cellular and molecular regulation of innate inflammatory responses. Cell Mol Immunol 1358(10):711–721. Nature Publishing GroupCrossRefGoogle Scholar
  43. 43.
    Nakaya Y et al (2017) AIM2-like receptors positively and negatively regulate the interferon response induced by cytosolic DNA. MBio 8(4):1–17CrossRefGoogle Scholar
  44. 44.
    Sun L et al (2013) Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type-I interferon pathway. Science 339(6121):786–791PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Kotsovolis G, Kallaras K (2010) The role of endothelium and endogenous vasoactive substances in sepsis. Hippokratia 14(2):88–93PubMedPubMedCentralGoogle Scholar
  46. 46.
    Janeway CA, Medzhitov R (2002) Innate immune recognition. Annu Rev Immunol 20(1):197–216PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Medzhitov R, Preston-Hurlburt P, Janeway CA (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388(6640):394–397PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Achek A, Yesudhas D, Choi S (2016) Toll-like receptors: promising therapeutic targets for inflammatory diseases. Arch Pharm Res 39(8):1032–1049. Pharmaceutical Society of KoreaPubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Gao W et al (2017) Inhibition of toll-like receptor signaling as a promising therapy for inflammatory diseases: a journey from molecular to nano therapeutics. Front Physiol 8(July):508PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Imhof BA, Jemelin S, Emre Y (2017) Toll-like receptors elicit different recruitment kinetics of monocytes and neutrophils in mouse acute inflammation. Eur J Immunol 47(6):1002–1008PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Mogensen TH (2009) Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev 22(2):240–273PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Blasius AL, Beutler B (2010) Intracellular toll-like receptors. Immunity 32(3):305–315. Elsevier IncPubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Pifer R et al (2011) UNC93B1 is essential for TLR11 activation and IL-12-dependent host resistance to Toxoplasma gondii. J Biol Chem 286(5):3307–3314PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Yarovinsky F (2014) Innate immunity to Toxoplasma gondii infection. Nat Rev Immunol 14(2):109–121. Nature Publishing GroupPubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Horng T, Medzhitov R (2001) Drosophila MyD88 is an adapter in the Toll signaling pathway. Proc Natl Acad Sci U S A 98(22):12654–12658PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Salvador B et al (2016) Modulation of endothelial function by Toll like receptors. Pharmacol Res 108:46–56PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Ahmed S et al (2013) TRIF-mediated TLR3 and TLR4 signaling is negatively regulated by ADAM15. J Immunol 190(5):2217–2228PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Lin X et al (2015) Effect of TLR4/MyD88 signaling pathway on expression of IL-1B and TNF- a in synovial fibroblasts from temporomandibular joint exposed to lipopolysaccharide. Mediat Inflamm 2015:329405Google Scholar
  59. 59.
    Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11(5):373–384. Nature Publishing GroupPubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Pryshchep O et al (2008) Vessel-specific toll-like receptor profiles in human medium and large arteries. Circulation 118(12):1276–1284PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Nagyoszi P et al (2010) Expression and regulation of toll-like receptors in cerebral endothelial cells. Neurochem Int 57(5):556–564PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Sturtzel C (2017) Endothelial cells. Adv Exp Med Biol 1003:71–91PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Xiao L, Liu Y, Wang N (2014) New paradigms in inflammatory signaling in vascular endothelial cells. Am J Physiol Heart Circ Physiol 306(3):H317–H325PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Card CM, Yu SS, Swartz MA (2014) Emerging roles of lymphatic endothelium in regulating adaptive immunity. J Clin Investig 124(3):943–952PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Pegu A et al (2008) Human lymphatic endothelial cells express multiple functional TLRs. J Immunol 180(5):3399–3405PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Khakpour S, Wilhelmsen K, Hellman J (2015) Vascular endothelial cell Toll-like receptor pathways in sepsis. Innate Immun 21(8):827–846PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Mazzucchelli I et al (2015) Expression and function of toll-like receptors in human circulating endothelial colony forming cells. Immunol Lett 168(1):98–104. Elsevier B.V.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Opitz B et al (2007) Extra- and intracellular innate immune recognition in endothelial cells. Thromb Haemost 96(6):756–766Google Scholar
  69. 69.
    Zheng GJ, Sun Q, Li YP (2009) Inflammation, endothelium, coagulation in sepsis. Chin Crit Care Med 21(9):573–576Google Scholar
  70. 70.
    Dauphinee SM, Karsan A (2006) Lipopolysaccharide signaling in endothelial cells. Lab Investig 86(1):9–22PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Gotsch U et al (1994) Expression of P-selectin on endothelial cells is upregulated by LPS and TNF-a in vivo. Cell Adhes Commun 2:7PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Gatheral T et al (2012) A key role for the endothelium in NOD1 mediated vascular inflammation: comparison to TLR4 responses. PLoS One 7(8):1–13CrossRefGoogle Scholar
  73. 73.
    Wilhelmsen K et al (2012) Activation of endothelial TLR2 by bacterial lipoprotein upregulates proteins specific for the neutrophil response. Innate Immun 18(4):602–616PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Zimmer S et al (2011) Activation of endothelial toll-like receptor 3 impairs endothelial function. Circ Res 108(11):1358–1366PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Faure E et al (2001) Bacterial lipopolysaccharide and IFN-γ induce Toll-like receptor 2 and Toll-like receptor 4 expression in human endothelial cells: role of NF-κB activation. J Immunol 166(3):2018–2024PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    El Kebir D et al (2015) Toll-like receptor 9 signaling regulates tissue factor and tissue factor pathway inhibitor expression in human endothelial cells and coagulation in mice. Crit Care Med 43(6):e179–e189PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Dunzendorfer S, Lee HK, Tobias PS (2004) Flow-dependent regulation of endothelial toll-like receptor 2 expression through inhibition of SP1 activity. Circ Res 95(7):684–691PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Bomfim GF et al (2014) Toll like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rat. Clin Sci 122(11):535–543CrossRefGoogle Scholar
  79. 79.
    Hernanz R et al (2015) Toll-like receptor 4 contributes to vascular remodelling and endothelial dysfunction in angiotensin II-induced hypertension. Br J Pharmacol 172(12):3159–3176PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Su X et al (2011) Oxidized low density lipoprotein induces bone morphogenetic protein-2 in coronary artery endothelial cells via toll-like receptors 2 and 4. J Biol Chem 286(14):12213–12220PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Pahwa R, Nallasamy P, Jialal I (2016) Toll-like receptors 2 and 4 mediate hyperglycemia induced macrovascular aortic endothelial cell inflammation and perturbation of the endothelial glycocalyx. J Diabetes Complications 30(4):563–572. Elsevier IncPubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Rajamani U, Jialal I (2014) Hyperglycemia induces toll-like receptor-2 and -4 expression and activity in human microvascular retinal endothelial cells: implications for diabetic retinopathy. J Diabetes Res 2014:7–10. Hindawi Publishing CorporationCrossRefGoogle Scholar
  83. 83.
    Franchi L et al (2010) Function of NOD-like receptors in microbial recognition and host defense. Cancer 227(1):106–128Google Scholar
  84. 84.
    Bertin J et al (1999) Human CARD4 protein is a novel CED-4/Apaf-1 cell death family member that activates NF-ƙB*. Biochemistry 274(19):12955–12958Google Scholar
  85. 85.
    Inohara N et al (1999) Nod1, and Apap-1-like activator of caspase-9 and nuclear factor-kB. J Biol Chem 274(21):14560–14567PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Ogura Y et al (2001) Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-??B. J Biol Chem 276(7):4812–4818PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Claes A et al (2015) NOD-like receptors: guardians of intestinal mucosal barriers. Physiology (Bethesda) 30:241–250Google Scholar
  88. 88.
    Motta V et al (2015) NOD-like receptors: versatile cytosolic sentinels. Physiol Rev 95(1):149–178PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Opitz B et al (2005) Nod1-mediated endothelial cell activation by Chlamydophila pneumoniae. Circ Res 96(3):319–326PubMedCrossRefPubMedCentralGoogle Scholar
  90. 90.
    Opitz B et al (2006) Listeria monocytogenes activated p38 MAPK and induced IL-8 secretion in a nucleotide-binding oligomerization domain 1-dependent manner in endothelial cells. J Immunol 176(1):484–490PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Oh HM et al (2005) Induction and localization of NOD2 protein in human endothelial cells. Cell Immunol 237(1):37–44PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Nagata E, Oho T (2016) Invasive Streptococcus mutans induces inflammatory cytokine production in human aortic endothelial cells via regulation of intracellular TLR2 and NOD2. Mol Oral Microbiol 32:131–141PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Manni M et al (2011) Muramyl dipeptide induces Th17 polarization through activation of endothelial cells. J Immunol 186(6):3356–3363PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Wan M et al (2015) E-selectin expression induced by Porphyromonas gingivalis in human endothelial cells via nucleotide-binding oligomerization domain-like receptors and Toll-like receptors. Mol Oral Microbiol 30(5):399–410PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Lin C et al (2017) Helix B surface peptide attenuates diabetic cardiomyopathy via AMPK-dependent autophagy. Biochem Biophys Res Commun 482(4):665–671. Elsevier LtdPubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Bergsbaken T, Fink SL, Cookson BT (2010) Pyroptosis: host cell death and inflammation. Nat Rev Microbiol 7(2):99–109CrossRefGoogle Scholar
  97. 97.
    Ghosh S et al (2017) The PYHIN protein p205 regulates the inflammasome by controlling Asc expression. J Immunol 199:ji1700823Google Scholar
  98. 98.
    Schumann RR et al (1998) Lipopolysaccharide activates caspase-1 (interleukin-1-converting enzyme) in cultured monocytic and endothelial cells. Blood 91(2):577–584PubMedPubMedCentralGoogle Scholar
  99. 99.
    Li Y et al (2017) Negative regulation of NLRP3 inflammasome by SIRT1 in vascular endothelial cells. Immunobiology 222(3):552–561. Elsevier GmbHPubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Chen Y et al (2015) Endothelial Nlrp3 inflammasome activation associated with lysosomal destabilization during coronary arteritis. Biochim Biophys Acta 853(2):396–408.CrossRefGoogle Scholar
  101. 101.
    Kinnunen K (2017) Lysosomal destabilization activates the NLRP3 inflammasome in human umbilical vein endothelial cells (HUVECs). J Cell Commun Signal 11(3):275–279PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Chen Y et al (2016b) Contribution of redox-dependent activation of endothelial Nlrp3 inflammasomes to hyperglycemia-induced endothelial dysfunction. J Mol Med (Berlin) 94(12):1335–1347CrossRefGoogle Scholar
  103. 103.
    Bleda S et al (2016) Elevated levels of triglycerides and vldl-cholesterol provoke activation of nlrp1 inflammasome in endothelial cells. Int J Cardiol 220:52–55. Elsevier Ireland LtdPubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Chen H et al (2016a) Cadmium induces NLRP3 inflammasome-dependent pyroptosis in vascular endothelial cells. Toxicol Lett 246:7–16. Elsevier Ireland LtdPubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Cheng KT et al (2017) Caspase-11 – mediated endothelial pyroptosis underlies endotoxemia-induced lung injury. J Clin Invest 7(26):1–12Google Scholar
  106. 106.
    XI H et al (2016) Caspase-1 inflammasome activation mediates homocysteine- induced pyrop-apoptosis in endothelial cells. Circ Res 165(7):1789–1802Google Scholar
  107. 107.
    Franchi L et al (2009) The inflammasome: a caspase-1 activation platform regulating immune responses and disease pathogenesis. Nat Immun 10(3):241CrossRefGoogle Scholar
  108. 108.
    Rathinam VAK et al (2010) The AIM2 inflammasome is essential for host-defense against cytosolic bacteria and DNA viruses. Nat Immunol 11(5):395–402PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Alekseeva AY et al (2016) Multiple ways of cfDNA reception and following ROS production in endothelial cells. Adv Exp Med Biol 924:127–131PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Hakimi M et al (2014) Inflammation-related induction of absent in melanoma 2 (AIM2) in vascular cells and atherosclerotic lesions suggests a role in vascular pathogenesis. J Vasc Surg 59(3):794–803.e2. Society for Vascular SurgeryPubMedCrossRefPubMedCentralGoogle Scholar
  111. 111.
    Singh VV et al (2013) Kaposi’s sarcoma-associated herpesvirus latency in endothelial and B cells activates gamma interferon-inducible protein 16-mediated inflammasomes. J Virol 87(8):4417–4431PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Opitz B et al (2009) Role of Toll-like receptors, NOD-like receptors and RIG-I-like receptors in endothelial cells and systemic infections. Thromb Haemost 102(6):1103–1109PubMedPubMedCentralGoogle Scholar
  113. 113.
    Matsumiya T, Stafforini DM (2010) Function and regulation of retinoic acid-inducible gene-I. Crit Rev Immunol 30(6):489–513PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Kato H, Takahasi K, Fujita T (2011) RIG-I-like receptors: cytoplasmic sensors for non-self RNA. Immunol Rev 243:91–98PubMedCrossRefPubMedCentralGoogle Scholar
  115. 115.
    Imaizumi T, Yoshida H, Satoh K (2004) Regulation of CX3CL1/fractalkine expression in endothelial cells. J Atheroscler Thromb 11(1):15–21PubMedCrossRefPubMedCentralGoogle Scholar
  116. 116.
    Asdonk T et al (2012) Endothelial RIG-I activation impairs endothelial function. Biochem Biophys Res Commun 420(1):66–71. Elsevier IncPubMedCrossRefPubMedCentralGoogle Scholar
  117. 117.
    Berghäll H et al (2006) The interferon-inducible RNA helicase, mda-5, is involved in measles virus-induced expression of antiviral cytokines. Microbes Infect 8(8):2138–2144PubMedCrossRefPubMedCentralGoogle Scholar
  118. 118.
    Hägele H et al (2009) Double-stranded RNA activates type i interferon secretion in glomerular endothelial cells via retinoic acid-inducible gene (RIG)-1. Nephrol Dial Transplant 24(11):3312–3318PubMedCrossRefPubMedCentralGoogle Scholar
  119. 119.
    Peyrefitte C et al (2006) Dengue virus infection of human microvascular endothelial cells from different vascular beds promotes both common and specific functional changes. J Med Virol 78(12):229–242PubMedCrossRefPubMedCentralGoogle Scholar
  120. 120.
    da Conceição TM et al (2013) Essential role of RIG-I in the activation of endothelial cells by dengue virus. Virology 435(2):281–292PubMedCrossRefPubMedCentralGoogle Scholar
  121. 121.
    Blank T et al (2016) Brain endothelial- and epithelial-specific interferon receptor chain 1 drives virus-induced sickness behavior and cognitive impairment. Immunity 44(4):901–912PubMedCrossRefPubMedCentralGoogle Scholar
  122. 122.
    Moser J et al (2016) Intracellular RIG-I signaling regulates TLR4-independent endothelial inflammatory responses to endotoxin. J Immunol 196(11):4681–4691PubMedCrossRefPubMedCentralGoogle Scholar
  123. 123.
    Margolis SR, Wilson SC, Vance RE (2017) Evolutionary origins of cGAS-STING signaling. Trends Immunol 38(10):733–743. Elsevier LtdPubMedCrossRefPubMedCentralGoogle Scholar
  124. 124.
    Liu Y et al (2014) Activated STING in a vascular and pulmonary syndrome. N Engl J Med 371(6):507–518PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Lio C-WJ et al (2016) cGAS-STING signaling regulates initial innate control of cytomegalovirus infection. J Virol.
  126. 126.
    Ma Z et al (2015) Modulation of the cGAS-STING DNA sensing pathway by gammaherpesviruses. Proc Natl Acad Sci 112(31):E4306–E4315PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Mao Y et al (2017) STING–IRF3 triggers endothelial inflammation in response to free fatty acid-induced mitochondrial damage in diet-induced obesity. Arterioscler Thromb Vasc Biol 37(5):920–929PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Yuan L et al (2017) Palmitic acid dysregulates the Hippo-YAP pathway and inhibits angiogenesis by inducing mitochondrial damage and activating the cytosolic DNA sensor cGAS-STING-IRF3 signaling. J Biol Chem.
  129. 129.
    Fullerton JN, Gilroy DW (2016) Resolution of inflammation: a new therapeutic frontier. Nat Rev Drug Discov 15(8):551–567. Nature Publishing GroupCrossRefPubMedGoogle Scholar
  130. 130.
    Fischetti F, Tedesco F (2017) Cross-talk between the complement system and endothelial cells in physiologic conditions and in vascular diseases. Autoimmunity 39(5):417–428PubMedCrossRefPubMedCentralGoogle Scholar
  131. 131.
    Carter AM (2012) Complement activation: an emerging player in the pathogenesis of cardiovascular disease. Scientifica 2012:402783PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Brunn GJ, Saadi S, Platt JL (2006) Differential regulation of endothelial cell activation by complement and interleukin 1{alpha}. Circ Res 96:793–800CrossRefGoogle Scholar
  133. 133.
    Karpman D et al (2015) Complement interactions with blood cells, endothelial cells and microvesicles in thrombotic and inflammatory conditions. Adv Exp Med Biol 865:19PubMedCrossRefPubMedCentralGoogle Scholar
  134. 134.
    Kilgore KS et al (1995) Enhancement by the complement membrane attack complex of tumor necrosis factor-alpha-induced endothelial cell expression of E-selectin and ICAM-1. J Immunol 155(3):1434–1441PubMedPubMedCentralGoogle Scholar
  135. 135.
    Proctor LM et al (2004) Comparative anti-inflammatory activities of antagonists to C3a and C5a receptors in a rat model of intestinal ischaemia/reperfusion injury. Br J Pharmacol 142(4):756–764PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Yin W et al (2007) Classical pathway complement activation on human endothelial cells. Mol Immunol 44(9):2228–2234PubMedCrossRefPubMedCentralGoogle Scholar
  137. 137.
    Riedl M et al (2017) Complement activation induces neutrophil adhesion and neutrophil-platelet aggregate formation on vascular endothelial cells. Kidney Int Rep 2(1):66–75. Elsevier IncPubMedCrossRefPubMedCentralGoogle Scholar
  138. 138.
    Dobó J et al (2014) Multiple roles of complement MASP-1 at the interface of innate immune response and coagulation. Mol Immunol 61(2):69–78. Elsevier LtdPubMedCrossRefPubMedCentralGoogle Scholar
  139. 139.
    Jani PK et al (2016) Complement MASP-1 enhances adhesion between endothelial cells and neutrophils by up-regulating E-selectin expression. Mol Immunol 75:38–47. Elsevier LtdPubMedCrossRefPubMedCentralGoogle Scholar
  140. 140.
    Ghesquiere B et al (2014) Metabolism of stromal and immune cells in health and disease. Nature 511(7508):167–176. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights ReservedPubMedCrossRefPubMedCentralGoogle Scholar
  141. 141.
    O’Neill LAJ, Hardie DG (2013) Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature 493(7432):346–355. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights ReservedPubMedCrossRefPubMedCentralGoogle Scholar
  142. 142.
    O’Neill LAJ, Pearce EJ (2016) Immunometabolism governs dendritic cell and macrophage function. J Exp Med 213(1):15–23. The Rockefeller University PressPubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Wong BW et al (2017) Endothelial cell metabolism in health and disease: impact of hypoxia. EMBO J 36(15):2187–2203PubMedCrossRefPubMedCentralGoogle Scholar
  144. 144.
    Rodríguez-Prados J-C et al (2010) Substrate fate in activated macrophages: a comparison between innate, classic, and alternative activation. J Immunol 185(1):605 LP–605614CrossRefGoogle Scholar
  145. 145.
    Vats D et al (2006) Oxidative metabolism and PGC-1β attenuate macrophage-mediated inflammation. Cell Metab 4(1):13–24PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Galván-Peña S, O’Neill LAJ (2014) Metabolic reprograming in macrophage polarization. Front Immunol 5:420PubMedPubMedCentralGoogle Scholar
  147. 147.
    Rossi F, Zatti M (1964) Changes in the metabolic pattern of polymorphonuclear leucocytes during phagocytosis. Br J Exp Pathol 45(5):548–559PubMedPubMedCentralGoogle Scholar
  148. 148.
    Oren R et al (1963) Metabolic patterns in three types of phagocytizing cells. J Cell Biol 17(3):487–501. The Rockefeller University PressPubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Fukuzumi M et al (1996) Endotoxin-induced enhancement of glucose influx into murine peritoneal macrophages via GLUT 1. Infect Immun 64(1):108–112PubMedPubMedCentralGoogle Scholar
  150. 150.
    Jha AK et al (2017) Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity 42(3):419–430. ElsevierCrossRefGoogle Scholar
  151. 151.
    Newsholme P et al (1986) Metabolism of glucose, glutamine, long-chain fatty acids and ketone bodies by murine macrophages. Biochem J 239(1):121–125PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Riganti C et al (2012) The pentose phosphate pathway: an antioxidant defense and a crossroad in tumor cell fate. Free Radic Biol Med 53(3):421–436PubMedCrossRefPubMedCentralGoogle Scholar
  153. 153.
    Semba H et al (2016) HIF-1α-PDK1 axis-induced active glycolysis plays an essential role in macrophage migratory capacity. Nat Commun 7(May):11635. Nature Publishing GroupPubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Palsson-McDermott EM et al (2015) Pyruvate Kinase M2 regulates Hif-1α activity and IL-1β induction, and is a critical determinant of the Warburg Effect in LPS-activated macrophages. Cell Metab 21(1):65–80PubMedPubMedCentralCrossRefGoogle Scholar
  155. 155.
    Tannahill GM et al (2013) Succinate is a danger signal that induces IL-1β via HIF-1α. Nature 496(7444):238–242PubMedPubMedCentralCrossRefGoogle Scholar
  156. 156.
    Palsson-Mcdermott EM, O’Neill LAJ (2013) The Warburg effect then and now: from cancer to inflammatory diseases. BioEssays 35(11):965–973PubMedCrossRefPubMedCentralGoogle Scholar
  157. 157.
    Németh B et al (2015) Abolition of mitochondrial substrate-level phosphorylation by itaconic acid produced by LPS-induced Irg1 expression in cells of murine macrophage lineage. FASEB J 30:286–300PubMedCrossRefPubMedCentralGoogle Scholar
  158. 158.
    Infantino V et al (2011) The mitochondrial citrate carrier: a new player in inflammation. Biochem J 438(3):433–436PubMedCrossRefPubMedCentralGoogle Scholar
  159. 159.
    Michelucci A et al (2013) Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. Proc Natl Acad Sci 110(19):7820–7825PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Mills EL et al (2017) Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages. Cell 167(2):457–470.e13. ElsevierCrossRefGoogle Scholar
  161. 161.
    Garaude J et al (2016) Mitochondrial respiratory chain adaptations in macrophages contribute to antibacterial host defence. Nat Immunol 17(9):1037–1045PubMedPubMedCentralCrossRefGoogle Scholar
  162. 162.
    Littlewood-Evans A et al (2016) GPR91 senses extracellular succinate released from inflammatory macrophages and exacerbates rheumatoid arthritis. J Exp Med 213:1655PubMedPubMedCentralCrossRefGoogle Scholar
  163. 163.
    Rubic T et al (2008) Triggering the succinate receptor GPR91 on dendritic cells enhances immunity. Nat Immunol 9(11):1261–1269. Nature Publishing GroupPubMedCrossRefPubMedCentralGoogle Scholar
  164. 164.
    Eelen G et al (2015) Endothelial cell metabolism in normal and diseased vasculature. Circ Res 116(7):1231–1244PubMedPubMedCentralCrossRefGoogle Scholar
  165. 165.
    De Bock K et al (2017) Role of PFKFB3-driven glycolysis in vessel sprouting. Cell 154(3):651–663. ElsevierGoogle Scholar
  166. 166.
    Groschner LN et al (2012) Endothelial mitochondria – less respiration, more integration. Pflugers Arch – Eur J Physiol 464(1):63–76CrossRefGoogle Scholar
  167. 167.
    Dagher Z et al (2001) Acute regulation of fatty acid oxidation and AMP-activated protein kinase in human umbilical vein endothelial cells. Circ Res 88(12):1276–1282PubMedCrossRefPubMedCentralGoogle Scholar
  168. 168.
    Mertens S et al (1990) Energetic response of coronary endothelial cells to hypoxia. Am J Physiol Heart Circ Physiol 258(3):H689 LP–H68H694CrossRefGoogle Scholar
  169. 169.
    Leopold JA et al (2003) Glucose-6-phosphate dehydrogenase overexpression decreases endothelial cell oxidant stress and increases bioavailable nitric oxide. Arterioscler Thromb Vasc Biol 23(3):411–417PubMedCrossRefPubMedCentralGoogle Scholar
  170. 170.
    Coulet F et al (2003) Identification of hypoxia-response element in the human endothelial nitric-oxide synthase gene promoter. J Biol Chem 278(47):46230–46240PubMedCrossRefPubMedCentralGoogle Scholar
  171. 171.
    Min J et al (2006) Hypoxia-induced endothelial NO synthase gene transcriptional activation is mediated through the tax-responsive element in endothelial cells. Hypertension 47(6):1189–1196PubMedCrossRefPubMedCentralGoogle Scholar
  172. 172.
    Weigand JE et al (2012) Hypoxia-induced alternative splicing in endothelial cells. PLoS One 7(8):e42697. Public Library of SciencePubMedPubMedCentralCrossRefGoogle Scholar
  173. 173.
    Xu Y et al (2014) Endothelial 6-phosphofructo-2-kinase (PFKFB3) plays a critical role in angiogenesis. Arterioscler Thromb Vasc Biol 34(6):1231–1239PubMedPubMedCentralCrossRefGoogle Scholar
  174. 174.
    Chan CK et al (2013) A-FABP and oxidative stress underlie the impairment of endothelium-dependent relaxations to serotonin and the intima-medial thickening in the porcine coronary artery with regenerated endothelium. ACS Chem Neurosci 4(1):122–129. American Chemical SocietyPubMedCrossRefPubMedCentralGoogle Scholar
  175. 175.
    Doddaballapur A et al (2014) Laminar shear stress inhibits endothelial cell metabolism via KLF2-mediated repression of PFKFB3. Arterioscler Thromb Vasc Biol 35(1):137–145PubMedCrossRefPubMedCentralGoogle Scholar
  176. 176.
    Folco EJ et al (2011) Hypoxia but not inflammation augments glucose uptake in human macrophages: implications for imaging atherosclerosis with 18fluorine-labeled 2-deoxy-D-glucose positron emission tomography. J Am Coll Cardiol 58(6):603–614PubMedCrossRefPubMedCentralGoogle Scholar
  177. 177.
    Cantelmo AR et al (2017) Inhibition of the glycolytic activator PFKFB3 in endothelium induces tumor vessel normalization, impairs metastasis, and improves chemotherapy. Cancer Cell 30(6):968–985. ElsevierCrossRefGoogle Scholar
  178. 178.
    Manthiram K et al (2017) The monogenic autoinflammatory diseases define new pathways in human innate immunity and inflammation. Nat Immunol 18(8):832–842. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights ReservedPubMedCrossRefPubMedCentralGoogle Scholar
  179. 179.
    Klen J et al (2015) NLRP3 inflammasome polymorphism and macrovascular complications in type 2 diabetes patients. J Diabetes Res 2015:616747PubMedPubMedCentralCrossRefGoogle Scholar
  180. 180.
    Miao ZM et al (2009) NALP3 inflammasome functional polymorphisms and gout susceptibility. Cell Cycle 8(1):27–30PubMedCrossRefPubMedCentralGoogle Scholar
  181. 181.
    French FMF Consortium (1997) A candidate gene for familial Mediterranean fever. Nat Genet 17(1):25–31CrossRefGoogle Scholar
  182. 182.
    Giancane G et al (2015) Evidence based recommendations for genetic diagnosis of familial Mediterranean fever. Ann Rheum Dis 74(4):635–641PubMedCrossRefPubMedCentralGoogle Scholar
  183. 183.
    Chu LH et al (2016) An updated view on the structure and function of PYRIN domains. Apoptosis 20(2):157–173CrossRefGoogle Scholar
  184. 184.
    Manukyan G, Aminov R (2016) Update on pyrin functions and mechanisms of familial Mediterranean fever. Front Microbiol 7(March):1–8Google Scholar
  185. 185.
    Gao W et al (2016) Site-specific phosphorylation and microtubule dynamics control Pyrin inflammasome activation. Proc Natl Acad Sci 113(33):E4857–E4866PubMedPubMedCentralCrossRefGoogle Scholar
  186. 186.
    Standing ASI et al (2017) Autoinflammatory periodic fever, immunodeficiency, and thrombocytopenia (PFIT) caused by mutation in actin-regulatory gene WDR1. J Exp Med 214(1):59–71PubMedPubMedCentralCrossRefGoogle Scholar
  187. 187.
    Kile BT et al (2007) Mutations in the cofilin partner Aip1/Wdr1 cause autoinflammatory disease and macrothrombocytopenia. Blood 110(7):2371–2380PubMedPubMedCentralCrossRefGoogle Scholar
  188. 188.
    Kim ML et al (2015) Aberrant actin depolymerization triggers the pyrin inflammasome and autoinflammatory disease that is dependent on IL-18, not IL-1β. J Exp Med 212(6):927–938PubMedPubMedCentralCrossRefGoogle Scholar
  189. 189.
    Agostini L et al (2004) NALP3 forms an IL-1β-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity 20(3):319–325PubMedCrossRefPubMedCentralGoogle Scholar
  190. 190.
    Mortimer L et al (2016) NLRP3 inflammasome inhibition is disrupted in a group of auto-inflammatory disease CAPS mutations. Nat Immunol 17(10):1176–1186. Nature Publishing GroupPubMedCrossRefPubMedCentralGoogle Scholar
  191. 191.
    Hsieh CW et al (2017) Elevated expression of the NLRP3 inflammasome and its correlation with disease activity in adult-onset still disease. J Rheumatol 44(8):1142–1150PubMedCrossRefPubMedCentralGoogle Scholar
  192. 192.
    Gopalarathinam R et al (2016) Adult onset Still’s disease: a review on diagnostic workup and treatment options. Case Rep Rheumatol 2016:1–6. Hindawi Publishing CorporationCrossRefGoogle Scholar
  193. 193.
    Magitta NF et al (2009) A coding polymorphism in NALP1 confers risk for autoimmune Addison’s disease and type 1 diabetes. Genes Immun 10(2):120–124PubMedCrossRefPubMedCentralGoogle Scholar
  194. 194.
    Pontillo A et al (2012) Polimorphisms in inflammasome genes are involved in the predisposition to systemic lupus erythematosus. Autoimmunity 45(4):271–278. Taylor & FrancisPubMedCrossRefPubMedCentralGoogle Scholar
  195. 195.
    Sui J et al (2012) NLRP1 gene polymorphism influences gene transcription and is a risk factor for rheumatoid arthritis in han chinese. Arthritis Rheum 64(3):647–654PubMedCrossRefPubMedCentralGoogle Scholar
  196. 196.
    Grandemange S et al (2017) A new autoinflammatory and autoimmune syndrome associated with NLRP1 mutations: NAIAD (NLRP1- associated autoinflammation with arthritis and dyskeratosis). Ann Rheum Dis 76(7):1191–1198PubMedCrossRefPubMedCentralGoogle Scholar
  197. 197.
    Zhong FL et al (2016) Germline NLRP1 mutations cause skin inflammatory and cancer susceptibility syndromes via inflammasome activation. Cell 167(1):187–202.e17PubMedCrossRefPubMedCentralGoogle Scholar
  198. 198.
    Canna SW et al (2015) An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat Genet 46(10):1140–1146CrossRefGoogle Scholar
  199. 199.
    Romberg N et al (2014) Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation. Nat Genet 165(7):1789–1802Google Scholar
  200. 200.
    Kawasaki Y et al (2016) Pluripotent cell-based phenotypic dissection identifies a high-frequency somatic NLRC4 mutation as a cause of autoinflammation. Arthritis Rheumatol 11(10):300–308Google Scholar
  201. 201.
    Goldbach-Mansky R et al (2006) Neonatal-onset multisystem inflammatory disease responsive to interleukin-1β inhibition. N Engl J Med 355(6):581–592PubMedPubMedCentralCrossRefGoogle Scholar
  202. 202.
    Freed D, Stevens EL, Pevsner J (2014) Somatic mosaicism in the human genome. Genes 5(4):1064–1094PubMedPubMedCentralCrossRefGoogle Scholar
  203. 203.
    Hoffman HM et al (2008) Efficacy and safety of rilonacept (Interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum 58(8):2443–2452PubMedCrossRefPubMedCentralGoogle Scholar
  204. 204.
    Lachmann HJ et al (2009) Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med 360(23):2416–2425PubMedCrossRefPubMedCentralGoogle Scholar
  205. 205.
    Meinzer U et al (2017) Interleukin-1 targeting drugs in familial Mediterranean fever: a case series and a review of the literature. Semin Arthritis Rheum 41(2):265–271. ElsevierCrossRefGoogle Scholar
  206. 206.
    Canna SW et al (2017) Life-threatening NLRC4-associated hyperinflammation successfully treated with IL-18 inhibition. J Allergy Clin Immunol 139(5):1698–1701PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Daiane Boff
    • 1
  • Caio Tavares Fagundes
    • 2
  • Remo Castro Russo
    • 3
  • Flavio Almeida Amaral
    • 1
    Email author
  1. 1.Laboratório de Imunofarmacologia, Departamento de Bioquímica e ImunologiaUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  2. 2.Laboratório de Interação Microrganismo-Hospedeiro, Departamento de MicrobiologiaUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  3. 3.Laboratório de Imunologia e Mecânica Pulmonar, Departamento de Fisiologia e BiofísicaUniversidade Federal de Minas GeraisBelo HorizonteBrazil

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