PT - JOURNAL ARTICLE AU - Lei Guo AU - Caiying Ye AU - Xiaojian Hao AU - Ru Zheng AU - Rui Ju AU - Danwei Wu AU - Lifeng Luo AU - Conghui Wang AU - Juan Li AU - Xiaoli Yu AU - Lei Zhu AU - Dechang Zhang TI - Carboxyamidotriazole Ameliorates Experimental Colitis by Inhibition of Cytokine Production, Nuclear Factor-κB Activation, and Colonic Fibrosis AID - 10.1124/jpet.112.192849 DP - 2012 Aug 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 356--365 VI - 342 IP - 2 4099 - http://jpet.aspetjournals.org/content/342/2/356.short 4100 - http://jpet.aspetjournals.org/content/342/2/356.full SO - J Pharmacol Exp Ther2012 Aug 01; 342 AB - Carboxyamidotrizole (CAI) has been reported to suppress the production of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β and be effective in rats with adjuvant arthritis. The aim of this study was to investigate the role of CAI in inflammatory bowel disease (IBD). We assessed the effect of CAI in dextran sodium sulfate-induced colitis. Inflammation was scored histologically, and potential mediators of IBD were assessed by immunohistochemical and molecular biochemical approaches. CAI-treated colitis animals revealed much fewer signs of colitis with significantly decreased macroscopic and microscopic scores than vehicle-treated animals. CAI inhibited the production of TNF-α, IL-1β, and IL-6 in serum, supernatant of peritoneal macrophages, and lamina propria. CAI also decreased the expression of intercellular adhesion molecule-1 in colonic tissues. Furthermore, CAI prevented nuclear factor-κB (NF-κB) activation and inhibitor of nuclear factor-κBα phosphorylation and degradation. In addition, CAI showed a beneficial effect on colonic fibrosis, possibly by reducing the production of the fibrogenic cytokine transforming growth factor-β. The results support that CAI administration is effective in ameliorating experimental colitis and preventing colonic fibrosis. The inhibition of proinflammatory cytokines and adhesion molecules and suppression of NF-κB activation seem to contribute to this effect.