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BACKGROUND Interleukin (IL)-22, a member of the IL-10 cytokine family, is the only known cytokine that is secreted by immune cells but does not target immune cells; it mainly targets epithelial cells. In this study, we aimed to determine whether IL-22 administration could activate the myocardial STAT3 (signal transducer and activator of transcription-3) signaling pathway, and thus prevent myocardial injury, in a mouse model of ischemia reperfusion injury. METHODS AND RESULTS We evaluated the STAT3 activation after IL-22 injection by Western blot analysis and immunostaining for phosphorylated STAT3 in the heart and found that STAT3 activation in heart tissue rapidly peaked after IL-22 injection. Coimmunostaining of phosphorylated STAT3 and α-actinin revealed that STAT3 activation occurred in cardiomyocytes after IL-22 administration. In heart tissue from intact mice, real-time PCR demonstrated significant expression of IL-22 receptor subunit 1, and coimmunostaining of IL-22 receptor subunit 1 and α-actinin showed IL-22 receptor subunit 1 expression in cardiomyocytes. In cultured cardiomyocytes, IL-22 activated STAT3, and we detected IL-22 receptor subunit 1 expression. Overall, these results indicated that IL-22 directly activated the myocardial IL-22-receptor subunit 1-STAT3 signaling pathway. Following ischemia reperfusion, compared with PBS-treated mice, IL-22-treated mice exhibited a significantly reduced infarct size, significantly reduced myocardial apoptosis, and significantly enhanced phosphorylated STAT3 expression. Moreover, heart tissue from IL-22-treated mice exhibited a significantly reduced expression ratio of phosphorylated p53 to p53. CONCLUSIONS Our present findings suggest that IL-22 directly activated the myocardial STAT3 signaling pathway and acted as a cardioprotective cytokine to ameliorate acute myocardial infarction after ischemia reperfusion.

背景

白细胞介素（IL）-22 是 IL-10 细胞因子家族的成员，是唯一已知由免疫细胞分泌但不针对免疫细胞的细胞因子；它主要针对上皮细胞。在这项研究中，我们旨在确定白细胞介素-22（IL-22）给药是否可以激活缺血再灌注损伤小鼠模型中的心肌 STAT3（信号转导和转录激活因子-3）信号通路，从而预防心肌损伤。

方法和结果

我们通过 Western blot 分析和心脏组织中磷酸化 STAT3 的免疫染色评估了 IL-22 注射后的 STAT3 激活情况，发现 IL-22 注射后心脏组织中 STAT3 激活迅速达到峰值。磷酸化 STAT3 和 α-辅肌动蛋白的共免疫染色显示，IL-22 给药后 STAT3 激活发生在心肌细胞中。在完整小鼠的心脏组织中，实时 PCR 显示 IL-22 受体亚基 1 的表达显著，IL-22 受体亚基 1 和 α-辅肌动蛋白的共免疫染色显示心肌细胞中存在 IL-22 受体亚基 1 的表达。在培养的心肌细胞中，IL-22 激活了 STAT3，我们检测到了 IL-22 受体亚基 1 的表达。总的来说，这些结果表明 IL-22 直接激活了心肌的 IL-22-受体亚基 1-STAT3 信号通路。与 PBS 处理的小鼠相比，缺血再灌注后，IL-22 处理的小鼠梗死面积明显减小，心肌细胞凋亡明显减少，磷酸化 STAT3 表达明显增强。此外，IL-22 处理的小鼠心脏组织中磷酸化 p53 与 p53 的表达比值明显降低。