TRIM24 调控STAT6 磷酸化介导的巨噬细胞M2 极化缓解病毒性心肌炎.

TRIM24 alleviates viral myocarditis by promoting STAT6 phosphorylation mediated macrophage M2 polarization.

Objective: To study the role and preliminary molecular mechanism of TRIM24 regulating macrophage polarization in viral myocarditis （VM）. Methods: VM mouse model was established by Coxsackie virus B3（ CVB3）, and expression of TRIM24 in myocardial tissue was detected. Cardiac inflammation level and polarization phenotype of cardiac infiltrating macrophages in a murine model of cardiac TRIM24 inhibition were detected in vivo. A polarization model of mouse bone marrow-derived macrophages（ BMDMs） in vitro was established to observe the role of TRIM24 inhibition in polarizing BMDMs to M1 and M2, as well as its effects on phagocytosis and bactericidal function of BMDMs. Effects of TRIM24 inhibition on total STAT6 protein level and phosphorylation were investigated. Results: TRIM24 was significantly highly expressed in myocardial tissue of VM mice （P<0.001）. Inhibition of TRIM24 expression in myocardium had an attenuating effect on VM and promoted polarization of cardiac infiltrating macrophages to M2. TRIM24 was significantly down-regulated in vitro during the polarization of BMDMs toward M2 （P<0.01）. Inhibition of TRIM24 expression significantly promoted macrophage polarization toward M2 type and inhibited polarization toward M1 type, accompanied by a significant increase in STAT6 phosphorylation levels （P<0.01）. Conclusion: TRIM24 regulates macrophage M2 polarization via activation of STAT6 signaling pathway to attenuate VM. [ABSTRACT FROM AUTHOR]

目的: 探讨TRIM24调控巨噬细胞极化在小鼠病毒性心肌炎（VM）中的作用及初步分子机制。方法: 建立柯 萨奇B3病毒（CVB3）诱导的VM小鼠模型, 检测心肌组织TRIM24表达。体内实验观察TRIM24抑制对VM小鼠心肌炎症及心 脏浸润巨噬细胞极化表型的影响。建立小鼠骨髓来源巨噬细胞（BMDMs）体外极化模型, 观察TRIM24抑制在BMDMs向M1及 M2极化中的作用, 及其对BMDMs吞噬和杀菌功能的影响。检测TRIM24抑制对STAT6总蛋白及磷酸化水平的影响。结果: TRIM24在VM小鼠心肌组织中显著高表达（P<0.001）, 抑制TRIM24能有效缓解VM, 并促进心脏浸润巨噬细胞向M2极化。体 外实验证实TRIM24在BMDMs向M2极化的过程中显著下调（P<0.01）, 抑制TRIM24表达能促进巨噬细胞向M2极化并抑制M1 表型, 同时伴随STAT6磷酸化水平显著升高（P<0.01）。结论: TRIM24通过激活STAT6信号通路调控巨噬细胞M2极化缓解 VM. [ABSTRACT FROM AUTHOR]

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