Department of Tuberculosis, Shandong Provincial Chest Hospital, Jinan, China.
FEBS Lett. 2019 Jun;593(12):1326-1335. doi: 10.1002/1873-3468.13438. Epub 2019 Jun 2.
To date, very little is known about the role of microRNA-21-5p (miR-21-5p) in Mycobacterium tuberculosis (M.tb)-infected macrophages. Here, we show that M.tb infection of RAW264.7 and THP-1 cells increases the expression of miR-21-5p. MiR-21-5p enhances M.tb survival and apoptosis, and attenuates the secretion of inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in M.tb-infected macrophages. Dual-luciferase reporter assay revealed that the 3'-UTR of B-cell lymphoma 2 (Bcl-2) or toll-like receptor 4 (TLR4) is a direct target of miR-21-5p. Enforced expressions of Bcl-2 or TLR4 partially attenuate the suppressive effects of miR-21-5p on cell viability and inflammatory cytokines, and effectively decrease bacterial burden. Therefore, the present study highlights a novel role for miR-21-5p in regulation of mycobacterial survival and inflammatory responses by targeting Bcl-2 and TLR4 in M.tb-infected macrophages.
迄今为止，人们对微小 RNA-21-5p（miR-21-5p）在结核分枝杆菌（M.tb）感染的巨噬细胞中的作用知之甚少。在这里，我们表明 RAW264.7 和 THP-1 细胞中的 M.tb 感染会增加 miR-21-5p 的表达。miR-21-5p 增强了 M.tb 的存活和细胞凋亡，并减弱了 M.tb 感染的巨噬细胞中炎症细胞因子（包括白细胞介素（IL）-1β、IL-6 和肿瘤坏死因子-α）的分泌。双荧光素酶报告基因检测显示 B 细胞淋巴瘤 2（Bcl-2）或 Toll 样受体 4（TLR4）的 3'-UTR 是 miR-21-5p 的直接靶标。Bcl-2 或 TLR4 的强制表达部分减弱了 miR-21-5p 对细胞活力和炎症细胞因子的抑制作用，并有效降低了细菌负荷。因此，本研究强调了 miR-21-5p 通过靶向 M.tb 感染的巨噬细胞中的 Bcl-2 和 TLR4 来调节分枝杆菌存活和炎症反应的新作用。
