• Yu-Hua Liao, Ni Xia, Su-Feng Zhou, Ting-Ting Tang, Xin-Xin Yan, Bing-Jie Lv, Shao-Fang Nie, Jing Wang, Yoichiro Iwakura, Hong Xiao, Jing Yuan, Harish Jevallee, Fen Wei, Guo-Ping Shi, and Xiang Cheng.
• Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
• J. Am. Coll. Cardiol. 2012 Jan 24;59(4):420-9.

ObjectivesThis study tested whether interleukin (IL)-17A is involved in the pathogenesis of mouse myocardial ischemia/reperfusion (I/R) injury and investigated the mechanisms.BackgroundInflammatory processes play a major role in myocardial I/R injury. We recently identified IL-17A as an important cytokine in inflammatory cardiovascular diseases such as atherosclerosis and viral myocarditis. However, its role in myocardial I/R injury remains unknown.MethodsThe involvement of IL-17A was assessed in functional assays in mouse myocardial I/R injury by neutralization/repletion or genetic deficiency of IL-17A, and its mechanism on cardiomyocyte apoptosis and neutrophil infiltration were further studied in vivo and in vitro.ResultsInterleukin-17A was elevated after murine left coronary artery ligation and reperfusion. Intracellular cytokine staining revealed that γδT lymphocytes but not CD4(+) helper T cells were a major source of IL-17A. Anti-IL-17A monoclonal antibody treatment or IL-17A knockout markedly ameliorated I/R injury, as demonstrated by reduced infarct size, reduced cardiac troponin T levels, and improved cardiac function. This improvement was associated with a reduction in cardiomyocyte apoptosis and neutrophil infiltration. In contrast, repletion of exogenous IL-17A induced the opposite effect. In vitro study showed that IL-17A mediated cardiomyocyte apoptosis through regulating the Bax/Bcl-2 ratio, induced CXC chemokine-mediated neutrophil migration and promoted neutrophil-endothelial cell adherence through induction of endothelial cell E-selectin and inter-cellular adhesion molecule-1 expression.ConclusionsIL-17A mainly produced by γδT cells plays a pathogenic role in myocardial I/R injury by inducing cardiomyocyte apoptosis and neutrophil infiltration.Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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