Abstract
Interleukin (IL)-17 (also known as IL-17A), as the signature cytokine of the newly described T helper 17 (Th17) cell population, is the founding member of a new subclass of cytokines that have highly proinflammatory properties. Recently there is accumulating evidence that stipulates the involvement of IL-17 in the pathogenesis of cardiovascular diseases via amplifying the inflammation induced by other cytokines in synergistic interactions. The present review provides a summary of the potential roles of IL-17 in the context derived from both animal models and clinical settings in cardiovascular diseases, and perspectives for IL-17-targeted cytokine therapy.
Similar content being viewed by others
References
Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136:2348–2357
Abbas AK, Murphy KM, Sher A (1996) Functional diversity of helper T lymphocytes. Nature 383:787–793
Murphy KM, Reiner SL (2002) The lineage decisions of helper T cells. Nat Rev Immunol 2:933–944
Romagnani S (1997) The Th1/Th2 paradigm. Immunol Today 18:263–266
Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123–1132
Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, Dong C (2005) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 6:1133–1141
Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A, Sallusto F, Napolitani G (2007) Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol 8:639–646
Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F (2007) Interleukins 1 beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 8:942–949
Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, Parente E, Filì L, Ferri S, Frosali F, Giudici F, Romagnani P, Parronchi P, Tonelli F, Maggi E, Romagnani S (2007) Phenotypic and functional features of human Th17 cells. J Exp Med 204:1849–1861
Bettelli E, Oukka M, Kuchroo VK (2007) TH-17 cells in the circle of immunity and autoimmunity. Nat Immunol 8:345–350
Dong C (2008) TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol 8:337–348
Weaver CT, Harrington LE, Mangan PR, Gavrieli M, Murphy KM (2006) Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity 24:677–688
Witowski J, Ksiazek K, Jörres A (2004) Interleukin-17: a mediator of inflammatory responses. Cell Mol Life Sci 61:567–579
Kawaguchi M, Kokubu F, Kuga H, Matsukura S, Hoshino H, Ieki K, Imai T, Adachi M, Huang SK (2001) Modulation of bronchial epithelial cells by IL-17. J Allergy Clin Immunol 108:804–809
Kim SR, Lee KS, Park SJ, Min KH, Lee KY, Choe YH, Lee YR, Kim JS, Hong SJ, Lee YC (2007) PTEN down-regulates IL-17 expression in a murine model of toluene di isocyanate-induced airway disease. J Immunol 179:6820–6829
Von Vietinghoff S, Ley K (2010) Interleukin 17 in vascular inflammation. Cytokine Growth Factor Rev 21:463–469
Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, Bamba T, Fujiyama Y (2003) Increased expression of interleukin 17 in inflammatory bowel disease. Gut 52:65–70
Zhao XF, Pan HF, Yuan H, Zhang WH, Li XP, Wang GH, Wu GC, Su H, Pan FM, Li WX, Li LH, Chen GP, Ye DQ (2010) Increased serum interleukin 17 in patients with systemic lupus erythematosus. Mol Biol Rep 37:81–85
Yuan FL, Li X, Lu WG, Zhao YQ, Li CW, Li JP, Sun JM, Xu RS (2012) Type 17 T-helper cells might be a promising therapeutic target for osteoporosis. Mol Biol Rep 39:771–774
Rouvier E, Luciani MF, Mattéi MG, Denizot F, Golstein P (1993) CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus Saimiri gene. J Immunol 150:5445–5456
Yao Z, Fanslow WC, Seldin MF, Rousseau AM, Painter SL, Comeau MR, Cohen JI, Spriggs MK (1995) Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor. Immunity 3:811–821
Yao Z, Timour M, Painter S, Fanslow W, Spriggs M (1996) Complete nucleotide sequence of the mouse CTLA 8 gene. Gene 168:223–225
Pappu BP, Angkasekwinai P, Dong C (2008) Regulatory mechanisms of helper T cell differentiation: new lessons learned from interleukin 17 family cytokines. Pharmacol Ther 117:374–384
Gaffen SL (2009) Structure and signalling in the IL-17 receptor family. Nat Rev Immunol 9:556–567
Kolls JK, Lindén A (2004) Interleukin-17 family members and inflammation. Immunity 21:467–476
Michel ML, Mendes-da-Cruz D, Keller AC, Lochner M, Schneider E, Dy M, Eberl G, Leite-de-Moraes MC (2008) Critical role of ROR-gammat in a new thymic pathway leading to IL-17-producing invariant NKT cell differentiation. Proc Natl Acad Sci U S A 105:19845–19850
Lockhart E, Green AM, Flynn JL (2006) IL-17 production is dominated by gamma delta T cells rather than CD4 T cells during Mycobacterium tuberculosis infection. J Immunol 177:4662–4669
Molet S, Hamid Q, Davoine F, Nutku E, Taha R, Pagé N, Olivenstein R, Elias J, Chakir J (2001) IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol 108:430–438
Lubberts E (2008) IL-17/Th17 targeting: on the road to prevent chronic destructive arthritis? Cytokine 41:84–91
Garrett-Sinha LA, John S, Gaffen SL (2008) IL-17 and the Th17 lineage in systemic lupus erythematosus. Curr Opin Rheumatol 20:519–525
Kuestner RE, Taft DW, Haran A, Brandt CS, Brender T, Lum K, Harder B, Okada S, Ostrander CD, Kreindler JL, Aujla SJ, Reardon B, Moore M, Shea P, Schreckhise R, Bukowski TR, Presnell S, Guerra-Lewis P, Parrish-Novak J, Ellsworth JL, Jaspers S, Lewis KE, Appleby M, Kolls JK, Rixon M, West JW, Gao Z, Levin SD (2007) Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F. J Immunol 179:5462–5473
Toy D, Kugler D, Wolfson M, Vanden Bos T, Gurgel J, Derry J, Tocker J, Peschon J (2006) Cutting edge: interleukin 17 signals through a heteromeric receptor complex. J Immunol 177:36–39
Gaffen SL (2008) An overview of IL-17 function and signaling. Cytokine 43:402–407
Shalom-Barak T, Quach J, Lotz M (1998) Interleukin-17-induced gene expression in articular chondrocytes is associated with activation of mitogen-activated protein kinases and NF-kappaB. J Biol Chem 273:27467–27473
Shen F, Gaffen SL (2008) Structure–function relationships in the IL-17 receptor: implications for signal transduction and therapy. Cytokine 41:92–104
Chang SH, Park H, Dong C (2006) Act1 adaptor protein is an immediate and essential signaling component of interleukin-17 receptor. J Biol Chem 281:35603–35607
Qian Y, Liu C, Hartupee J, Altuntas CZ, Gulen MF, Jane-Wit D, Xiao J, Lu Y, Giltiay N, Liu J, Kordula T, Zhang QW, Vallance B, Swaidani S, Aronica M, Tuohy VK, Hamilton T, Li XX (2007) The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease. Nat Immunol 8:247–256
Li X (2008) Act1 modulates autoimmunity through its dual functions in CD40L/BAFF and IL-17 signaling. Cytokine 41:105–113
Schwandner R, Yamaguchi K, Cao Z (2000) Requirement of tumor necrosis factor receptor-associated factor (TRAF) 6 in interleukin 17 signal transduction. J Exp Med 191:1233–1240
Fang NX, Yao YT, Shi CX, Li LH (2010) Attenuation of ischemia-reperfusion injury by Sevoflurane postconditioning involves protein kinase B and glycogen synthase kinase 3 beta activation in isolated rat hearts. Mol Biol Rep 37:3763–3769
Yang J, Zhang X-D, Yang J, Ding J-W, Liu Z-Q, Li S-G, Yang R (2010) The cardioprotective effect of fluvastatin on ischemic injury via down-regulation of toll-like receptor 4. Mol Biol Rep 38:3037–3044
Ke JJ, Yu FX, Rao Y, Wang YL (2011) Adenosine postconditioning protects against myocardial ischemia-reperfusion injury though modulate production of TNF-alpha, prevents activation of transcription factor NF-kappaB. Mol Biol Rep 38:531–553
Wang LS, Yan JJ, Tang NP, Zhu J, Wang YS, Wang QM, Tang JJ, Wang MW, Jia EZ, Yang ZJ, Huang J (2011) A polymorphism in the visfatin gene promoter is related to decreased plasma levels of inflammatory markers in patients with coronary artery diseases. Mol Biol Rep 38:819–825
Hansson GK, Libby P, Schonbeck U, Yan ZQ (2002) Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circ Res 91:281–291
Hansson GK, Libby P (2006) The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol 6:508–519
van der Wal AC, Das PK, Bentz van de Berg D, van der Loos CM, Becker AE (1989) Atherosclerotic lesions in humans. In situ immunophenotypic analysis suggesting an immune mediated response. Lab Invest 61:166–170
Kovanen PT, Kaartinen M, Paavonen T (1995) Infiltrates of activated mast cells at the site of coronary atheromatous erosion or rupture in myocardial infarction. Circulation 92:1084–1088
Erbel C, Chen L, Bea F, Wangler S, Celik S, Lasitschka F, Wang Y, Böckler D, Katus HA, Dengler TJ (2009) Inhibition of IL-17A attenuates atherosclerotic lesion development in apoE-deficient mice. J Immunol 183:8167–8175
Song L, Schindler C (2004) IL-6 and the acute phase response in murine atherosclerosis. Atherosclerosis 177:43–51
Eid RE, Rao DA, Zhou J, Lo SF, Ranjbaran H, Gallo A, Sokol SI, Pfau S, Pober JS, Tellides G (2009) Interleukin-17 and interferon-gamma are produced concomitantly by human coronary artery-infiltrating T cells and act synergistically on vascular smooth muscle cells. Circulation 119:1424–1432
Cheng X, Yu X, Ding YJ, Fu QQ, Xie JJ, Tang TT, Yao R, Chen Y, Liao YH (2008) The Th17/Treg imbalance in patients with acute coronary syndrome. Clin Immunol 127:89–97
Xie JJ, Wang J, Tang TT, Chen J, Gao XL, Yuan J, Zhou ZH, Liao MY, Yao R, Yu X, Wang D, Cheng Y, Liao YH, Cheng X (2010) The Th17/Treg functional imbalance during atherogenesis in ApoE (–/–) mice. Cytokine 49:185–193
de Boer OJ, van der Meer JJ, Teeling P, van der Loos CM, Idu MM, van Maldegem F, Aten J, van der Wal AC (2010) Differential expression of interleukin-17 family cytokines in intact and complicated human atherosclerotic plaques. J Pathol 220:499–508
Smith E, Prasad KMR, Butcher M, Dobrian A, Kolls JK, Ley K, Galkina E (2010) Blockade of IL-17A results in reduced atherosclerosis in apoE-deficient mice. Circulation 121:1746–1755
Chen S, Shimada K, Crother T, Zhang W, Huang G, Arditi M (2010) IL-17A is proatherogenic in high-fat diet-induced and Chlamydia pneumoniae infection-accelerated atherosclerosis in mice. J Immunol 185:5619–5627
Taleb S, Romain M, Ramkhelawon B, Uyttenhove C, Pasterkamp G, Herbin O, Esposito B, Perez N, Yasukawa H, Snick JV, Yoshimura A, Tedgui A, Mallat Z (2009) Loss of SOCS3 expression in T cells reveals a regulatory role for interleukin-17 in atherosclerosis. J Exp Med 206:2067–2077
Ribichini F, Wijns W (2002) Acute myocardial infarction: reperfusion treatment. Heart 88:298–305
Frangogiannis NG, Smith CW, Entman ML (2002) The inflammatory response in myocardial infarction. Cardiovasc Res 53:31–47
Huang Y, Rabb H, Womer Kl (2007) Ischemia-reperfusion and immediate T cell responses. Cell Immunol 248:4–11
Linfert D, Chowdhry T, Rabb H (2009) Lymphocytes and ischemia-reperfusion injury. Transplant Rev 23:1–10
Edgerton C, Crispín JC, Moratz CM, Bettelli E, Oukka M, Simovic M, Zacharia A, Egan R, Chen J, Dalle Lucca JJ, Juang YT, Tsokos GC (2009) IL-17 producing CD4+ T cells mediate accelerated ischemia/reperfusion-induced injury in autoimmunity-prone mice. Clin Immunol 130:313–321
Lu L, Li G, Rao J, Pu L, Yu Y, Wang X, Zhang F (2009) In vitro induced CD4(+)CD25(+)Foxp3(+) Tregs attenuate hepatic ischemia-reperfusion injury. Int Immunopharmacol 9:549–552
Xia N, Tang TT, Liu Y, Zhou SF, Yan XX, Zhu ZF, Nie SF, Liu J, Zhang WC, Yang Y, Liao YH, Cheng X (2010) The role of IL- 17 in ischemia reperfusion injury. J Clin Cardiol 26:130–132
Afzali B, Lombardi G, Lechler RI, Lord GM (2007) The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease. Clin Exp Immunol 148:32–46
Feng W, Li W, Liu W, Wang F, Li Y, Yan W (2009) IL-17 induces myocardial fibrosis and enhances RANKL/OPG and MMP/TIMP signaling in isoproterenol-induced heart failure. Exp Mol Pathol 87:212–218
Liu W, Feng W, Wang F, Li W, Zhou B, Gao C, Li Y, Kong Y, Ma M, Fu S (2008) Adenovirus-mediated ICOSIg gene transfer alleviates cardiac remodeling in experimental autoimmune myocarditis. Immunol Cell Biol 86:659–665
Yuan J, Yu M, Lin QW, Cao AL, Yu X, Dong JH, Wang JP, Zhang JH, Wang M, Guo HP, Cheng X, Liao YH (2010) Th17 cells contribute to viral replication in coxsackievirus B3-induced acute viral myocarditis. J Immunol 185:4004–4010
Qing K, Weifeng W, Fan Y, Yuluan Y, Yu P, Yanlan H (2011) Distinct different expression of Th17 and Th9 cells in coxsackie virus B3-induced mice viral myocarditis. Virol J 8:267
Yang F, Wu WF, Yan YL, Pang Y, Kong Q, Huang YL (2011) Expression of IL-23/Th17 pathway in a murine model of coxsackie virus B3-induced viral myocarditis. Virol J 8:301
Fan Y, Yuluan Y, Qing K, Yu P, Yanlan H (2011) Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of coxsackievirus b3-induced viral myocarditis reduces myocardium inflammation. Virol J 8:17
Baldeviano GC, Talor MV, Srinivasan S, Bedja D, Zhang D, Gabrielson K, Iwakura Y, Rose NR, Cihakova D (2010) Interleukin-17A is dispensable for myocarditis but essential for the progression to dilated cardiomyopathy. Circ Res 106:1646–1655
Acknowledgment
This work was supported in part by the National Natural Science Foundation of China (Grant No. 81170133) and the Natural Science Foundation of Hubei Province, China (Grant No. 2011CDB179).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ding, HS., Yang, J., Yang, J. et al. Interleukin-17 contributes to cardiovascular diseases. Mol Biol Rep 39, 7473–7478 (2012). https://doi.org/10.1007/s11033-012-1580-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-012-1580-5