Abstract
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.