Abstract: Objective This study is designed to explore the regulations of carboxyamidotriazole (CAI) on kinds of inflammatory factors in vitro and its underlying mechanisms. Method Peritoneal macrophages were incubated with different concentrations (5-40 μmol/L), and then cell viabilities were evaluated by MTT assay. Cells were pretreated with CAI (5-40 μmol/L), LPS was then added, and cells were incubated for 18 h. NO and TNF-α levels were determined with Griess reagent and ELISA kit, respectively. The iNOS expression and NF-κB activation were detected by Western blot method. Result The rat peritoneal macrophage viablilties were not affected at the concentrations of CAI used. CAI (5-40 μmol/L) was found to reduce NO (p< 0.01, p< 0.001) and TNF-α production (p< 0.05, p< 0.01) in a dose-dependent manner. CAI was also found to inhibit the LPS-induced expression of iNOS and degradation of IκBα in rat peritoneal macrophages. Conclusion The findings of the present study suggest that CAI has suppressive effect on iNOS expression, and this inhibitory effect of CAI was found to be associated with NF-κB inactivation via the blockade of IκBα phosphorylation.

Key words: Carboxyamidotriazole, Macrophage, iNOS, NF-κB Activation