Lipopolysaccharide promotes the recovery of dextran sulfate sodium- induced colitis by regulating the Toll-like receptor 4 signaling pathway

Abstract

Abstract Background: The roles of lipopolysaccharide (LPS) and Toll-like receptor 4 (TLR4) in the recovery of colitis were further investigated. Methods: Human normal colonic epithelial cells with low, normal and high expression levels of TLR4 were constructed using lentiviral transfection, and subsequently incubated with LPS. Cells were divided into low + LPS, normal + LPS and high + LPS groups. The expression levels of cytokines were examined using quantitative real-time PCR and ELISA. Cell migration was observed using wound healing assays. In vivo, mice with dextran sulfate sodium (DSS)-induced colitis were treated with LPS and a TLR4 inhibitor, TAK-242. Changes in body weight, colonic length and the histopathology of mice were analyzed. Results: The expression levels of TLR4 in the high + LPS group were significantly increased in a time-dependent manner. Compared with the normal + LPS group, the expression levels of TNF-α, IL-6, IL-8 and IL-1β in the high + LPS group were significantly decreased, while the expression levels of IL-10 were reversed. The migratory ability of cells with high TLR4 expression was markedly increased. In vivo, compared with the TAK-242 group, mice with DSS-induced colitis in the LPS group exhibited a positive weight increase, longer colon length and reduced inflammatory infiltration, and the expression levels of TNF-α and IL-6 were significantly reduced, and the expression levels of IL-10 were significantly increased. Conclusion: LPS promoted the release of cytokines and auxiliary stimulating molecules to regulate the inflammatory response and promote the recovery of colitis by regulating the TLR4 pathway.