IL-38 attenuates myocardial ischemia-reperfusion injury by inhibiting macrophage inflammation.

Abstract

Reperfusion therapy is the most effective approach to resolve coronary occlusion, but myocardial injury caused by excessive inflammation during myocardial ischemia-reperfusion will also pose a new threat to health. Our prior study revealed the expression pattern of interleukin-38 (IL-38)in the peripheral blood serum of patients with ischemic cardiomyopathy and the role of IL-38 in acute myocardial infarction in mice. However, its role and potential mechanisms in myocardial ischemia/reperfusion injury (MIRI)remain to be determined. The left anterior descending artery of C57BL/6 mice was transiently ligated to induce theMIRI model. We found that MIRI induced the expression of endogenous IL-38, which was mainly produced by locally infiltrating macrophages. Overexpression of IL-38 in C57BL/6 mice attenuated inflammatory injury and decreased myocardial apoptosis after myocardial ischemia-reperfusion. Furthermore, IL-38 inhibited lipopolysaccharide-induced macrophage inflammation in vitro. Cardiomyocytes cocultured with the supernatant of IL-38- and troponin I-treated macrophages showed a lower rate of apoptosis than controls. IL-38 attenuates MIRIby inhibiting macrophage inflammation. This inhibitory effect may be partially achieved by inhibiting the activation of NOD-like receptor pyrin domain-related protein 3inflammasome, resulting in decreased expression of inflammatory factors and reduced cardiomyocyte apoptosis.