Essandoh Kobina, Li Yutian, Huo Jiuzhou, Fan Guo-Chang
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Shock. 2016 Aug;46(2):122-31. doi: 10.1097/SHK.0000000000000604.
Monocytes and macrophages are important components of the immune system, specialized in either removing pathogens as part of innate immunity or contributing to adaptive immunity through antigen presentation. Essential to such functions is classical activation (M1) and alternative activation (M2) of macrophages. M1 polarization of macrophages is characterized by production of pro-inflammatory cytokines, antimicrobial and tumoricidal activity, whereas M2 polarization of macrophages is linked to immunosuppression, tumorigenesis, wound repair, and elimination of parasites. MiRNAs are small non-coding RNAs with the ability to regulate gene expression and network of cellular processes. A number of studies have determined miRNA expression profiles in M1 and M2 polarized human and murine macrophages using microarray and RT-qPCR arrays techniques. More specifically, miR-9, miR-127, miR-155, and miR-125b have been shown to promote M1 polarization while miR-124, miR-223, miR-34a, let-7c, miR-132, miR-146a, and miR-125a-5p induce M2 polarization in macrophages by targeting various transcription factors and adaptor proteins. Further, M1 and M2 phenotypes play distinctive roles in cell growth and progression of inflammation-related diseases such as sepsis, obesity, cancer, and multiple sclerosis. Hence, miRNAs that modulate macrophage polarization may have therapeutic potential in the treatment of inflammation-related diseases. This review highlights recent findings in miRNA expression profiles in polarized macrophages from murine and human sources, and summarizes how these miRNAs regulate macrophage polarization. Last, therapeutic potential of miRNAs in inflammation-related diseases through modulation of macrophage polarization is also discussed.
单核细胞和巨噬细胞是免疫系统的重要组成部分,专门负责作为固有免疫的一部分清除病原体,或通过抗原呈递促进适应性免疫。巨噬细胞的经典激活(M1)和替代激活(M2)对于这些功能至关重要。巨噬细胞的M1极化特征在于促炎细胞因子的产生、抗菌和杀肿瘤活性,而巨噬细胞的M2极化与免疫抑制、肿瘤发生、伤口修复和寄生虫清除有关。微小RNA(miRNA)是一类小型非编码RNA,具有调节基因表达和细胞过程网络的能力。许多研究已经使用微阵列和逆转录定量聚合酶链反应(RT-qPCR)阵列技术确定了M1和M2极化的人和小鼠巨噬细胞中的miRNA表达谱。更具体地说,miR-9、miR-127、miR-155和miR-125b已被证明可促进M1极化,而miR-124、miR-223、miR-34a、let-7c、miR-132、miR-146a和miR-125a-5p通过靶向各种转录因子和衔接蛋白诱导巨噬细胞中的M2极化。此外,M1和M2表型在细胞生长和炎症相关疾病(如败血症、肥胖症、癌症和多发性硬化症)的进展中发挥着独特作用。因此,调节巨噬细胞极化的miRNA可能在炎症相关疾病的治疗中具有治疗潜力。本综述重点介绍了来自小鼠和人类来源的极化巨噬细胞中miRNA表达谱的最新发现,并总结了这些miRNA如何调节巨噬细胞极化。最后,还讨论了miRNA通过调节巨噬细胞极化在炎症相关疾病中的治疗潜力。