LAUSR

Background Acute myocardial infarction (AMI) is followed by an acute inflammation involving inflammasome activation, thereby inducing cardiac dysfunction. Interleukin‐17A (IL‐17A) involves in many inflammatory diseases, but its roles in inflammation following AMI are still obscure. The aim of this study is to investigate the roles of IL‐17A in the inflammatory response following AMI and its underlying mechanisms. Methods and results NLRP3 inflammasome and AMPK&agr;/p38MAPK/ERK1/2 signaling pathway were significantly activated under the induction of IL‐17A in mouse peritoneal macrophages, which could be inhibited by AMPK inhibitor compound C (CC). Both p38MAPK and ERK1/2 inhibitors could partially inhibit the activation of NLRP3 inflammasome in macrophages treated by IL‐17A. In vivo, IL‐17A knockout not only decreased the infiltration of macrophages and the activation of NLRP3 inflammasome and AMPK&agr;/p38MAPK/ERK1/2 signaling pathway in ischemic myocardium, but also improved cardiac function and reduced infarction size after the ligation of descending segment from left coronary artery for 3 days in mice, while IL‐17A administration further aggravated the myocardial ischemic injury, which were prevented by CC administration. Conclusion IL‐17A aggravates inflammatory response during AMI by inducing macrophages infiltration and activating NLRP3 inflammasome through AMPK&agr;/p38MAPK/ERK1/2 pathway. HighlightsIL‐17A activates NLRP3 inflammasome and increases IL‐1&bgr; release via AMPK&agr;/p38MAPK/ERK1/2 pathway in macrophages.IL‐17A contributes to myocardial ischemic injury by facilitating macrophages infiltration and inflammasome activation in ischemic myocardium.AMPK&agr; activation plays an unexpected pro‐inflammatory role in the inflammation induced by IL‐17A during acute ischemia.