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.
Footnotes
This work was supported by the Special Program for Key Basic Research of the Ministry of Science and Technology, China [Grant 2009ZX09102-049/2009ZX09303-008]; the National Natural Science Foundation of China [Grant 30873075]; and the Special Foundation of the President of the Chinese Academy of Medical Science [Grant 2009PY01/2010PY08/2010PYZ19].
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
ABBREVIATIONS:
- UC
- ulcerative colitis
- CD
- Crohn's disease
- IBD
- inflammatory bowel disease
- CAI
- carboxyamidotriazole
- DSS
- dextran sodium sulfate
- ICAM-1
- intercellular adhesion molecule-1
- IκB
- inhibitor of nuclear factor-κB
- IKK
- IκB kinase
- IL
- interleukin
- LPS
- lipopolysaccharide
- NF-κB
- nuclear factor-κB
- PBS
- phosphate-buffered saline
- PEG 400
- polyethylene glycol 400
- SASP
- sulfasalazine
- TGF
- transforming growth factor
- TNF-α
- tumor necrosis factor-α
- VCAM-1
- vascular cell adhesion molecule-1.
- Received February 12, 2012.
- Accepted May 1, 2012.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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