P8: Dietary nitrite induces TFF3 and attenuates inflammation in experimental colitis

Abstract

Nitric oxide (NO) and its derivative nitrite NO 2 - have evolved as important mediators in the prevention of gastrointestinal diseases. A central event in inflammatory bowel disease is the disruption of the mucosal homeostasis. Trefoil peptides (TFFs) are emerging as key mediators in the defense and repair of the gastrointestinal mucosa as they play a key role in epithelial restitution, the initial step in the wound healing process. Here we examined the anti-inflammatory effects of dietary NO 2 - and the potential role of TFFs in a model of ulcerative colitis: the dextran sulfate sodium (DSS) model. Balb/c mice were treated with DSS (2%, drinking water) in the presence of sodium nitrite (1 mg/kg, drinking water), or with 2.5% DSS for 3 days prior to administration of sodium nitrite. At the end of the experiment (7–10 days) the extent of inflammation was measured by the colon length, the disease activity index (DAI), and colonic expression of the intestinal trefoil factor (TFF3). In addition, colon epithelial cells (SW480) were treated with increasing doses of Na NO 2 - (1μM-1 mM), and the mRNA levels of TFF3 were evaluated. Finally, the effect of Na NO 2 - (1 μM−1 mM) was also analyzed in an in vitro wound healing assay (SW480 cells, 0–48 h). DSS groups (2% and 2.5%) developed colitis as evident by a marked reduction in colon length as well as an increase in DAI, compared to the control groups. In both groups nitrite reduced DAI score but the prevention of the decrease in colon length was only significant with 2% of DSS. The colonic levels of TFF3 increased in the presence of 2% DSS but decreased with 2.5% DSS administration. NO 2 - treatment increased TFF3 levels in both groups, but the effect was higher with 2% DSS. A dose-dependent response in mRNA expression of TFF3 was observed in SW480 cells after NO 2 - treatment; where a maximum increase in the expression was reached with 1–10 μM of nitrite. Interestingly, these results mirrored those obtained in the epithelial wound healing model in which nitrite increased the speed of repair. In conclusion, our results show that the dietary administration of nitrite reduces inflammation and improves clinical symptoms in DSS-induced colitis. This protection may involve regulation of the epithelial restitution process, as indicated by the increase in the healing process and the expression of TFF3 by dietary concentrations of nitrite. Disclosure Nothing to disclose.