Toll-like receptor 4 () deficiency aggravates dextran sulfate sodium (DSS)-induced intestinal injury by down-regulating , and .

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 ()-knockout mice (-KO) were used as dextran sulfate sodium (DSS)-induced colitis models to explore the role of 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 ( agonist) and -KO. When compared to WT mice, , , , , , and α significantly decreased and and have increased in the gut of -KO mice. , , , and 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, , , , , , and 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 ( agonistic monoclonal antibody) played the opposite role in colon cancer cells treated with DSS.

CONCLUSIONS

had a repairing effect on DSS-induced intestinal damage and it up-regulate , and . and enhanced DSS-induced colon injury in mice, but might have little to do with signaling.