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• W2994776331 abstract "Background: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes long-lasting inflammation and ulcers in the human digestive tract. The repair role of TLR4 in the intestinal epithelium is still unknown. Methods: By comparing to wild-type (WT) mice, Toll-like receptor 4 ( TLR4 )-knockout mice ( TLR4 -KO) were used as dextran sulfate sodium (DSS)-induced colitis models to explore the role of TLR4 signaling in intestinal injury. High-throughput RNA-Seq, RT-qPCR and ELISA were performed to screen and verify key differences in gut genes between WT and TLR4-KO mice. Functional study of core dysregulated factors was performed in intestinal cell lines. Results: We found that DSS-induced intestinal injury was aggravated by LPS ( TLR4 agonist) and TLR4- KO. When compared to WT mice, IL6 , CCL2 , CSF3 , IL11 , Ccnb1 , Ccnd1 and TNF-α significantly decreased and Fas and FasL have increased in the gut of TLR4- KO mice. IL6 , CCL2 , CSF3 , Fas and FasL have all increased in CT-26 cells treated with LPS. Combined with the above data and KEGG enrichment, it can be assumed that TLR4- KO might aggravate DSS-induced intestinal damage by attenuating cell cycle, cytokine-cytokine receptor interaction, and Toll-like receptor signaling pathway, and enhancing the apoptosis pathway. In the functional study of core dysregulated factors, it was found that LPS, IL6 , IL11 , CSF3 , CCL2 , S100A8 , S100A9 and Mmp3 have improved viability of colon cancer cell lines and decreased apoptosis rate of mouse colon cancer cells when these were treated with DSS. However, Jo-2 ( Fas agonistic monoclonal antibody) played the opposite role in colon cancer cells treated with DSS. Conclusions: TLR4 had a repairing effect on DSS-induced intestinal damage and it up-regulate IL6 , CCL2 and CSF3 . Fas and FasL enhanced DSS-induced colon injury in mice, but might have little to do with TLR4 signaling." @default.
• W2994776331 created "2019-12-26" @default.
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• W2994776331 date "2019-12-01" @default.
• W2994776331 modified "2023-10-16" @default.
• W2994776331 title "Toll-like receptor 4 (TLR4) deficiency aggravates dextran sulfate sodium (DSS)-induced intestinal injury by down-regulating IL6, CCL2 and CSF3" @default.
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• W2994776331 doi "https://doi.org/10.21037/atm.2019.12.28" @default.
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