| OBJECTIVES:Although numerous studies have indicated that inflammation plays a crucial role in the pathogenesis of myocardial ischemia/reperfusion injury, the mechanisms triggering the inflammatory actions in ischemic myocardium are not yet fully understood. Tumor necrosis factor-a-inducible protein8(TNFAIP8) family consisting of four members:TNFAIP8, TNFAIP8L1(TNF-alpha-induced protein8-like1, TIPE1), TIPE2, and TIPE3, are recently identified proteins, which are thought to regulate cellular and immune homeostasis. However, so far it is unknown the expression patterns of NOD2in the heart and the contribution of TNFAIP8to the pathogenesis of myocardial ischemia/reperfusion injury. Therefore, the present study was designed to explore the possible role of TNFAIP8family in the development and progression of myocardial ischemia/reperfusion injury.METHODS:Adult male C57BL/6J mice (WT) and NOD2-/-mice (25g-30g) were used in the experiments. Mice were randomly divided into several groups including sham and operation group, left anterior descending coronary artery ligation for30minutes and release the thread and reperfusion for3.6.12,24,48hours respectively. Outcomes of myocardial injury were assessed by HE staining and NBT staining. Expression and distribution of TNFAIP8family proteins were detected by immunohistochemistry, mRNA and protein expression were examined by Western blot and real time RT-PCR analyses. In vitro study, different kinds of cells including myocardial cells, fibroblast, endothelial cells and macrophages were treated by the model of oxygen-glucose deprivation (OGD).RESULTS:We found that proinflammatory factors including the levels of TNF-α, IL-1β, IL-6and MCP-1were increased after ischemia and reperfusion in mouse hearts. Furthermore, NOD2-/-mice exhibited reduced TNF-α, IL-6and MCP-1levels after myocardial ischemia/reperfusion injury. Meanwhile, among TNFAIP8family, TIPE2expression was significantly increased in ischemic heart. Furthermore, NOD2-/-mice exhibited more elevated TIPE2levels after myocardial ischemia/reperfusion injury. In in vitro study, TIPE2was signifantly enhanced in macrophages under OGD condition rather than myocardial cells, fibroblast or endothelial cells, indicating that inflammatory cells infiltration mainly contributes to the upregulation of TIPE2in ischemic hearts.CONCLUSIONS:Our results suggest that TIPE2is associated with myocardial ischemia/reperfusion injury and a direct casual link between NOD2and TIPE2in the pathogenesis of myocardial ischemia/reperfusion injury. |
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