Cytokine Tumor Necrosis Factor Alpha Induces Intestinal Epithelial Barrier Dysfunction.

BACKGROUND AND AIMS: Epithelial barrier dysfunction is involved in a number of diseases in the body. The mechanism is to be further understood. The present study aimed to investigate the role of one of the common microbial products, flagellin (FGN), in the induction of intestinal epithelial barrier dysfunction. METHODS: We collected the colon epithelium specimens from 40 patients with ulcerative colitis (UC), 40 patients with Crohn's disease (CD) and 40 healthy volunteers. The expression of toll like receptors (TLR)5 of the specimens was assessed by RT-PCR and western blotting. The expression of tumor necrosis factor alpha (TNFα) and its role in compromising the barrier function in the intestinal epithelial cells, T84 cells, were observed by a cell culture model. RESULTS: The results showed that the expression of TLR5 was observed in the colon epithelium of healthy subjects that was increased in UC patients and further increased in CD patients. Treating T84 cells with FGN increased the expression of TNFα in the cells that caused the T84 cell apoptosis as well as compromised the T84 monolayer barrier function, which could be prevented by knocking down the gene of TNFα in T84 cells. CONCLUSIONS: We conclude that the human colon epithelial cells express detectable TLR5 that is increased in patients with CD and UC. The exposure to FGN can increase the expression of TNFα that further compromises the intestinal epithelial barrier function.