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.

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]