Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.
J Pharmacol Exp Ther. 2012 Aug;342(2):356-65. doi: 10.1124/jpet.112.192849. Epub 2012 May 2.
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.
羧甲氮唑（CAI）已被报道可抑制肿瘤坏死因子-α（TNF-α）和白细胞介素（IL）-1β的产生，并在佐剂性关节炎大鼠中有效。本研究旨在探讨 CAI 在炎症性肠病（IBD）中的作用。我们评估了 CAI 在葡聚糖硫酸钠诱导的结肠炎中的作用。通过组织学评分评估炎症，并用免疫组织化学和分子生化方法评估 IBD 的潜在介质。与 vehicle 处理的动物相比，CAI 处理的结肠炎动物的结肠炎体征明显减少，宏观和微观评分显著降低。CAI 抑制了血清、腹腔巨噬细胞上清液和固有层中 TNF-α、IL-1β 和 IL-6 的产生。CAI 还降低了结肠组织中细胞间黏附分子-1 的表达。此外，CAI 可预防核因子-κB（NF-κB）激活和核因子-κBα磷酸化和降解。此外，CAI 对结肠纤维化具有有益作用，可能通过减少致纤维化细胞因子转化生长因子-β的产生。结果支持 CAI 给药可有效改善实验性结肠炎和预防结肠纤维化。抑制促炎细胞因子和黏附分子以及抑制 NF-κB 激活似乎对此作用有贡献。
