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Carboxyamidotriazole ameliorates experimental colitis by inhibition of cytokine production, nuclear factor-κB activation, and colonic fibrosis.

Abstract
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.
AuthorsLei Guo, Caiying Ye, Xiaojian Hao, Ru Zheng, Rui Ju, Danwei Wu, Lifeng Luo, Conghui Wang, Juan Li, Xiaoli Yu, Lei Zhu, Dechang Zhang
JournalThe Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 342 Issue 2 Pg. 356-65 (Aug 2012) ISSN: 1521-0103 [Electronic] United States
PMID22553216 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Interleukin-1beta
  • Interleukin-6
  • NF-kappa B
  • Triazoles
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • carboxyamido-triazole
  • Dextran Sulfate
Topics
  • Animals
  • Colitis (blood, drug therapy, metabolism, pathology)
  • Colon (drug effects, metabolism, pathology)
  • Dextran Sulfate
  • Fibrosis
  • Inflammation (blood, drug therapy, metabolism, pathology)
  • Inflammatory Bowel Diseases (blood, drug therapy, metabolism, pathology)
  • Intercellular Adhesion Molecule-1 (metabolism)
  • Interleukin-1beta (blood, metabolism)
  • Interleukin-6 (blood, metabolism)
  • Macrophages, Peritoneal (drug effects, metabolism, pathology)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mucous Membrane (drug effects, metabolism, pathology)
  • NF-kappa B (antagonists & inhibitors, metabolism)
  • Phosphorylation (drug effects)
  • Proteolysis (drug effects)
  • Triazoles (pharmacology)
  • Tumor Necrosis Factor-alpha (blood, metabolism)

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