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
朱良宇 1李雪琴 1张欣 1殷国泉 1张苑 1吕坤1
作者信息
- 1. 皖南医学院第一附属医院弋矶山医院中心实验室,芜湖 241001
- 折叠
摘要
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
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 phagocy-tosis and bactericidal function of BMDMs.Effects of TRIM24 inhibition on total STAT6 protein level and phosphorylation were investi-gated.Results:TRIM24 was significantly highly expressed in myocardial tissue of VM mice(P<0.001).Inhibition of TRIM24 expres-sion 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 signifi-cantly 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.
关键词
TRIM24/巨噬细胞极化/病毒性心肌炎Key words
TRIM24/Macrophage polarization/Viral myocarditis引用本文复制引用
基金项目
国家自然科学基金(82072370)
安徽省自然科学基金杰青项目(2108085J44)
出版年
2024
国家科技期刊平台
NSTL
万方数据