miR-642a-5p increases glucocorticoid sensitivity by suppressing the TLR4 signalling pathway in THP-1 cells.
miR-642a-5p increases glucocorticoid sensitivity by suppressing the TLR4 signalling pathway in THP-1 cells.
复制标题
DOI：
10.1016/j.bbrep.2022.101356
复制
发表时间：
2022-12
影响因子：
2.7
通讯作者：
Miao, Yinglei
中科院分区：
文献类型：
--
作者：
Luo, Juan;Wang, Yijie;Dong, Xiangqian;Wang, Wen;Mu, Yanju;Sun, Yang;Zhang, Fengrui;Miao, Yinglei
关键词：
溃疡性结肠炎（UC）的发病率逐年上升，糖皮质激素（GC）耐药性（GCR）是UC诱导缓解失败的常见原因。我们之前的研究表明，miR-642a-5p在UC伴GCR中表达下调，提示miR-642a-5p可能与GC反应有关。因此，我们研究了miR-642a-5p调控THP-1细胞GC反应的机制。我们发现，miR-642a-5p模拟物和DEX治疗后，细胞核中糖皮质激素受体（GR）和细胞质中NF-κB p65和p50的表达水平升高（P < 0.05）。miR-642a-5p模拟物转染THP-1细胞后，可与地塞米松（DEX）协同降低脂多糖（LPS）诱导的炎症因子TNF-α、IL-1β、IL-6、IL-12水平（P < 0.05）。生物信息学分析和荧光素酶报告基因检测证实TLR4是miR-642a-5p的靶基因。miR-642a-5p mimic预处理增强了DEX对LPS诱导的TLR4的抑制作用，抑制了细胞表面TLR4的表达（P < 0.05）。此外，miR-642a-5p进一步阻止NF-κB P65的核输入，抑制ERK、p38和JNK的磷酸化。这些结果表明，miR-642a-5p可以通过抑制THP-1细胞中的TLR4信号通路来抑制炎症。它还强调了TLR4信号通路作为抗炎症的潜在治疗靶点。miR-642a-5p可抑制LPS诱导的TLR4信号通路，增加THP-1细胞的糖皮质激素敏感性。
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. miR-642a-5p can inhibit the TLR4 signalling pathway induced by LPS and increase the glucocorticoid sensitivity in THP-1 cells.
登录
查看更多内容
miR-642a-5p通过EEF2部分介导脂多糖对人肺微血管内皮细胞的影响。
影响因子：
2.6
作者：
Fei L;Sun G;You Q
通讯作者：
You Q
影响因子：
5.6
作者：
De Iudicibus S;Lucafò M;Vitulo N;Martelossi S;Zimbello R;De Pascale F;Forcato C;Naviglio S;Di Silvestre A;Gerdol M;Stocco G;Valle G;Ventura A;Bramuzzo M;Decorti G
通讯作者：
Decorti G
DOI：
10.1164/rccm.201304-0775oc
发表时间：
2013-11-15
影响因子：
24.7
作者：
Goleva, Elena;Jackson, Leisa P.;Leung, Donald Y. M.
通讯作者：
Leung, Donald Y. M.
影响因子：
9.8
作者：
Ng, Siew C.;Kaplan, Gilaad G.;Sung, Joseph J. Y.
通讯作者：
Sung, Joseph J. Y.
影响因子：
4.6
作者：
He X;Wei Z;Wang J;Kou J;Liu W;Fu Y;Yang Z
通讯作者：
Yang Z