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miR-642a-5p increases glucocorticoid sensitivity by suppressing the TLR4 signalling pathway in THP-1 cells

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机构： [1]Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, Kunming Medical University, Kunming, China [2]Department of Intensive Care Unit, The First Affiliated Hospital of Kunming Medical University, Kunming, China

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关键词： miR-642a-5p Toll-like receptor 4 Glucocorticoid sensitivity Glucocorticoid resistance Ulcerative colitis

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The incidence rate of ulcerative colitis (UC) is increasing annually, and glucocorticoid (GC) resistance (GCR) is a common cause of UC-induced remission failure. Our previous studies have shown that the expression of miR-642a-5p is downregulated in UC with GCR, suggesting that miR-642a-5p may be related to the GC response. Therefore, we investigated the mechanism by which miR-642a-5p regulates the GC response in THP-1 cells. We found that after treatment with miR-642a-5p mimics and DEX, the expression levels of glucocorticoid receptor (GR) in the nucleus and NF-κB p65 and p50 in the cytoplasm were increased (P < 0.05). miR-642a-5p mimics transfected into THP-1 cells could synergize with dexamethasone (DEX) to reduce lipopolysaccharide (LPS)-induced inflammatory factor levels such as TNF-α, IL-1β, IL-6 and IL-12 (P < 0.05). Bioinformatics analysis and luciferase reporter assays confirmed that TLR4 is a target gene of miR-642a-5p. miR-642a-5p mimic pretreatment enhanced the inhibitory effect of DEX on TLR4 induced by LPS and inhibited the expression of TLR4 on the cell surface (P < 0.05). Additionally, miR-642a-5p further prevented the nuclear import of NF-κB P65 and inhibited the phosphorylation of ERK, p38 and JNK. These results suggest that miR-642a-5p can inhibit the inflammation by suppressing the TLR4 signalling pathway in THP-1 cells. It also highlights the TLR4 signalling pathway as a potential therapeutic target in anti-inflammation.© 2022 Published by Elsevier B.V.

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最新[2023]版：

Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

影响因子： 2.3 最新[2023版] 2.4 最新五年平均 0 出版当年[2021版] 0 出版当年五年平均 0 出版前一年[2020版] 2.7 出版后一年[2022版]

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第一作者机构： [1]Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, Kunming Medical University, Kunming, China

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通讯机构： [1]Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, Kunming Medical University, Kunming, China [*1]Department of Gastroenterology, Yunnan Province Clinical Research Center for Digestive Diseases, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, China

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