RT Journal Article SR Electronic T1 Carboxyamidotriazole Ameliorates Experimental Colitis by Inhibition of Cytokine Production, Nuclear Factor-κB Activation, and Colonic Fibrosis JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 356 OP 365 DO 10.1124/jpet.112.192849 VO 342 IS 2 A1 Lei Guo A1 Caiying Ye A1 Xiaojian Hao A1 Ru Zheng A1 Rui Ju A1 Danwei Wu A1 Lifeng Luo A1 Conghui Wang A1 Juan Li A1 Xiaoli Yu A1 Lei Zhu A1 Dechang Zhang YR 2012 UL http://jpet.aspetjournals.org/content/342/2/356.abstract 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.