Resveratrol ameliorates intestinal barrier defects and inflammation in colitic mice and intestinal cells.

This study is aimed to investigate the ameliorative effect of resveratrol in a dextran sodium sulfate (DSS)-induced colitis mouse model and intestinal Caco-2 cells, focusing on neutrophil infiltration and tight junction (TJ) barriers. DSS administration caused body weight loss (day8, control 104±1, DSS 72±2 % , p<0.05), shortening of colon length (control 5.1±0.1, DSS 3.8±0.1 cm, p<0.05), pro-inflammatory cytokines increase-including interleukin (IL)-1β (control 1.0±0.2, DSS 58.5±29.6 arbitrary unit (AU), p<0.05), IL-6 (control 1.0±0.3, DSS 312±82 AU, p<0.05), and chemokine motif ligand 2 (CXCL-2, a murine IL-8 homolog, control 1.0±0.4, DSS 696±262 AU, p<0.05), decreased TJ proteins (e.g. occludin, control 1.0±0.05, DSS 0.11±0.03 AU, p<0.05) and neutrophil infiltration (control 1.2±0.2, DSS 25.9±1.1 cells, p<0.05). Supplemental resveratrol (0.1% (w/w) in the diet) partially or totally reversed these symptoms (body weight change 100±1, colon length 4.6±0.1; IL-1β 5.9±1.8, IL-6 10±3, CXCL-2 14±7, occludin 0.76±0.06, neutrophil infiltration 9.3±0.7, p<0.05). Pretreatment of intestinal Caco-2 cells with resveratrol suppressed the TNF-α-induced production of IL-8 (control 1.00±0.04, TNFα 3.40±0.16, TNFα+Res 1.81±0.28 AU, p<0.05) and phosphorylation of the inflammatory signaling molecules including NF-κB, extracellular signal-regulated kinase and stress c-Jun N-terminal protein kinase. Collectively, the reduction of TJ barrier defect and IL-8 in intestinal cells, leading to reduced neutrophil infiltration into colonic tissues, appears to be one of the central mechanisms for the resveratrol-mediated effect.