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hsa_circ_0001204 通过 TLR4/NF-κB 信号通路调节结核分枝杆菌感染的巨噬细胞的炎症反应。

Hsa_circ_0001204 modulates inflammatory response of macrophages infected by Mycobacterium tuberculosis via TLR4/NF-κB signalling pathway.

机构信息

Department of Tuberculosis, Hangzhou Chest Hospital Affiliated to Zhejiang University Medical College, Hangzhou, China.

The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.

出版信息

Clin Exp Pharmacol Physiol. 2023 Feb;50(2):132-139. doi: 10.1111/1440-1681.13716. Epub 2022 Nov 23.

Abstract

Circular RNAs (circRNAs) play a vital role in the regulation of Mycobacterium tuberculosis (M.tb) by macrophages. In this project, the potential role of hsa_circ_0001204 in M.tb-infected macrophages is explored. Hsa_circ_0001204 was determined in the patients with tuberculosis (TB) and M.tb-infected macrophages. Its effect on the survival of M.tb and the apoptosis and inflammation of M.tb-infected macrophages was evaluated. Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signalling was detected by western blotting and immunofluorescence. TB patients and M.tb-infected THP-1 cells showed the significant downregulation of hsa_circ_0001204. Upregulating hsa_circ_0001204 reduced M.tb survival and suppressed the apoptosis and inflammatory response of THP-1 cells. The TLR4/NF-κB signalling pathway could be inhibited by hsa_circ_0001204 overexpression, which was activated by M.tb-infection. Hsa_circ_0001204 confers protective effects in M.tb-infected THP-1 cells, at least partly via the inhibition of TLR4/NF-κB signalling pathway.

摘要

环状 RNA(circRNAs)在巨噬细胞中调控结核分枝杆菌(M.tb)中发挥着重要作用。本项目探索了 hsa_circ_0001204 在感染 M.tb 的巨噬细胞中的潜在作用。在结核患者(TB)和感染 M.tb 的巨噬细胞中检测到 hsa_circ_0001204。评估了其对 M.tb 存活以及感染 M.tb 的巨噬细胞凋亡和炎症的影响。通过 Western blot 和免疫荧光检测 Toll 样受体 4/核因子-κB(TLR4/NF-κB)信号通路。TB 患者和感染 M.tb 的 THP-1 细胞中 hsa_circ_0001204 的表达显著下调。上调 hsa_circ_0001204 减少 M.tb 的存活并抑制 THP-1 细胞的凋亡和炎症反应。TLR4/NF-κB 信号通路可被 hsa_circ_0001204 过表达抑制,而 hsa_circ_0001204 的激活是由 M.tb 感染引起的。hsa_circ_0001204 赋予感染 M.tb 的 THP-1 细胞保护作用,至少部分通过抑制 TLR4/NF-κB 信号通路。

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