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 Guo, Lei
A1 Ye, Caiying
A1 Hao, Xiaojian
A1 Zheng, Ru
A1 Ju, Rui
A1 Wu, Danwei
A1 Luo, Lifeng
A1 Wang, Conghui
A1 Li, Juan
A1 Yu, Xiaoli
A1 Zhu, Lei
A1 Zhang, Dechang
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.