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miR-18b-5p 通过促进炎症反应下调 HIF-1α,有利于巨噬细胞清除

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

机构信息

The State Key Laboratory of Agricultural Microbiology, Wuhan, Hubei 430070, China.

College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.

出版信息

ACS Infect Dis. 2021 Apr 9;7(4):800-810. doi: 10.1021/acsinfecdis.0c00650. Epub 2021 Mar 11.

Abstract

The modulation of the interaction between macrophages and () through microRNA during 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 -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 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 -cell interaction mechanism and provide a potential target to control infection.

摘要

在 感染过程中,通过 microRNA 调节巨噬细胞与 ()之间的相互作用越来越引起研究人员的关注。然而,microRNA-18b-5p(miR-18b)的潜在作用尚未阐明。本研究发现,miR-18b 在时间和剂量依赖性方式下在 感染的巨噬细胞系(THP-1 和 RAW264.7)中下调。此外,当 miR-18b 模拟物和抑制剂以及缺氧诱导因子 1α 的小干扰 RNA(si-HIF-1α)分别或组合转染到巨噬细胞中时,发现 miR-18b 靶向缺氧诱导因子 1α(HIF-1α)。在 感染过程中,miR-18b 表达的降低促进了 HIF-1α 的表达,导致促炎细胞因子(如 IL-6)的产生增加,从而导致宿主细胞中细菌的存活减少。此外,miR-18b 抑制剂激活了 p38 MAPK 和 NF-κB p65 的磷酸化。我们的研究结果扩展了对 细胞相互作用机制的现有认识,并为控制 感染提供了一个潜在的靶标。

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