MicroRNA-18b-5p Downregulation Favors Mycobacterium tuberculosis Clearance in Macrophages via HIF-1α by Promoting an Inflammatory Response

作者：Tingting Zhu, Han Liu, Li Su, Xuekai Xiong, Jieru Wang, Yao Xiao, Yifan Zhu, Yongchong Peng, Ali Dawood, Changmin Hu, Xi Chen, Huanchun Chen, Yingyu Chen, Aizhen Guo · 发表于：ACS Infectious Diseases · 年份：2021 · DOI：10.1021/acsinfecdis.0c00650 · 被引用次数：25 · 研究领域：MicroRNA in disease regulation、Tuberculosis Research and Epidemiology、RNA modifications and cancer

High Resolution Image Download MS PowerPoint Slide The modulation of the interaction between macrophages and Mycobacterium tuberculosis ( M.tb ) through microRNA during M.tb infection is increasingly capturing the attention of researchers. However, the potential role of microRNA-18b-5p (miR-18b) is not elucidated yet. In this study, miR-18b was found to be downregulated in M.tb -infected macrophage cell lines (THP-1 and RAW264.7) in time- and dose-dependent manners. Furthermore, when the miR-18b mimic and inhibitor and small interfering RNA hypoxia-inducible factor 1α (si-HIF-1α) were transfected into the macrophages separately or in combination, it was found that miR-18b targeted hypoxia-inducible factor 1α (HIF-1α). During M.tb infection, the decrease in the expression of miR-18b facilitated HIF-1α expression, which led to the increased production of pro-inflammatory cytokines, such as IL-6, resulting in decreased bacterial survival in the host cells. Moreover, the phosphorylation of p38 MAPK and NF-κB p65 was activated by the miR-18b inhibitor. Our findings expand the current understanding of the M.tb –cell interaction mechanism and provide a potential target to control M.tb infection.