Effect of Autophagy Inducer pp242 on Intestinal Barrier Dysfunction Induced by Tumor Necrosis Factor-α / 胃肠病学

ABSTRACT

Intestinal barrier dysfunction and autophagy abnormality play important roles in the mechanism of inflammatory bowel disease, however, whether autophagy has effect on intestinal barrier dysfunction has not been reported.Aims: To explore the effect of autophagy inducer pp242 on intestinal barrier dysfunction induced by tumor necrosis factor-α (TNF-α).Methods: Model of intestinal epithelial monolayer barrier was established with Caco-2 cells in Transwell chambers, and then randomly divided into four groups control group (without any intervention), TNF-α group (10 ng/mL TNF-α), pp242 group (1 μmol/L pp242), TNF-α+pp242 group (10 ng/mL TNF-α+1 μmol/L pp242).The intestinal barrier function was evaluated by transepithelial electrical resistance (TEER) and flux of FITC-dextran.The protein expressions of autophagy related protein LC3B-Ⅱ and p62 were detected by Western blotting.Results: Compared with control group, TEER was significantly decreased (P<0.05), flux of FITC-dextran, protein expressions of LC3B-Ⅱ and p62 were significantly increased in TNF-α group (P<0.05).Compared with TNF-α group, TEER was significantly increased (P<0.05), protein expression of LC3B-Ⅱ was significantly increased (P<0.05) while protein expression of p62 was significantly decreased in TNF-α+pp242 group (P<0.05).Conclusions: Autophagy inducer pp242 relieves TNF-α-induced intestinal epithelial barrier dysfunction via activating autophagy flux.