Interleukin-17A contributes to myocardial ischemia/reperfusion injury by regulating cardiomyocyte apoptosis and neutrophil infiltration

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Abstract

Objectives: This study tested whether interleukin (IL)-17A is involved in the pathogenesis of mouse myocardial ischemia/reperfusion (I/R) injury and investigated the mechanisms. Background: Inflammatory 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. Methods: The 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. Results: Interleukin-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. AntiIL-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. Conclusions: IL-17A mainly produced by γδT cells plays a pathogenic role in myocardial I/R injury by inducing cardiomyocyte apoptosis and neutrophil infiltration. © 2012 American College of Cardiology Foundation.

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Liao, Y. H., Xia, N., Zhou, S. F., Tang, T. T., Yan, X. X., Lv, B. J., … Cheng, X. (2012). Interleukin-17A contributes to myocardial ischemia/reperfusion injury by regulating cardiomyocyte apoptosis and neutrophil infiltration. Journal of the American College of Cardiology, 59(4), 420–429. https://doi.org/10.1016/j.jacc.2011.10.863

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