The State Key Laboratory of Agricultural Microbiology, Wuhan, Hubei 430070, China.
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
ACS Infect Dis. 2021 Apr 9;7(4):800-810. doi: 10.1021/acsinfecdis.0c00650. Epub 2021 Mar 11.
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.
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。
