microRNAs (miRNAs) play a crucial role in tissue development and the pathology of various diseases. However, the effects and roles of miRNAs in macrophage polarization have yet to be investigated. In this study, we analyzed and compared the miRNA expression profiles of bone marrow-derived macrophages (BMDMs) with two distinct polarizing conditions (classical macrophage activation 'M1' and alternative activation 'M2') using miRNA microarray. In total, 109 miRNAs were differentially expressed between M1 and M2. The differential expression of selected miRNAs was validated by real-time qRT-PCR: miR-181a, miR-155-5p, miR-204-5p and miR-451 were upregulated (fold change >2, P<0.05) and miR-125-5p, miR-146a-3p, miR-143-3p and miR-145-5p were downregulated (fold change <-2, P<0.05) in M1 compared with M2. In conclusion, our study may be useful for exploring the precise roles of miRNAs in macrophage differentiation and polarized activation processes in the future.
Macrophage infiltration is a hallmark feature of viral myocarditis. As studies have shown that microRNA-155 regulates the differentiation of macrophages, we aimed to investigate the role of microRNA-155 in VM. We report that silencing microRNA-155 protects mice from coxsackievirus B3 induced myocarditis. We found that microRNA-155 expression was upregulated and localized primarily in heart-infiltrating macrophages and CD4+ T lymphocytes during acute myocarditis. In contrast with wildtype (WT) mice, microRNA-155−/− mice developed attenuated viral myocarditis, which was characterized by decreased cardiac inflammation and decreased intracardiac CD45+ leukocytes. Hearts of microRNA-155−/− mice expressed decreased levels of the IFN-γ and increased levels of the cytokines IL-4 and IL-13. Although total CD4+ and regulatory T cells were unchanged in miR-155−/− spleen proportionally, the activation of T cells and CD4+ T cell proliferation in miR-155−/− mice were significantly decreased. Beyond the acute phase, microRNA-155−/− mice had reduced mortality and improved cardiac function during 5 weeks of follow-up. Moreover, silencing microRNA-155 led to increased levels of alternatively-activated macrophages (M2) and decreased levels of classically-activated macrophages (M1) in the heart. Combined, our studies suggest that microRNA-155 confers susceptibility to viral myocarditis by affecting macrophage polarization, and thus may be a potential therapeutic target for viral myocarditis.
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