8-（Tosylamino）quinoline inhibits macrophage-mediated inflammation by suppressing NF-KB signaling

• Published in: 中国药理学报：英文版 Vol. 33; no. 8; pp. 1037 - 1046
• Main Author: Yongwoo JUNG Se Eun BYEON Dae Sung YOO Yong Gyu LEE Tao YU Yanyan YANG Ji Hye KIM Eunji KIM Deok JEONG Man Hee RHEE Eui Su CHOUNG Sungyoul HONG Jae Youl CliO
• Format: Journal Article
• Language: English
• Published: 2012
• Subjects: NF-KB; 介导; 信号分子; 喹啉; 炎症反应; 甲苯; 腹腔巨噬细胞; 酰氨基
• ISSN: 1671-4083

Aim： The macrophage-mediated inflammatory response may contribute to the development of cancer, diabetes, atherosclerosis and septic shock. This study was to characterize several new compounds to suppress macrophage-mediated inflammation. Methods： Peritoneal macrophages from C57BL/6 male mice and RAW264.7 cells were examined. Anti-inflammatory activity was evalu- ated in the cells exposed to lipopolysaccharide （LPS）. The mechanisms of the anti-inflammatory activity were investigated via measur-ing transcription factor activation in response to specific signals and via assaying the activities of the target kinases. Results： Of 7 candidate compounds tested, 8-（tosylamino）quinoline （8-TQ, compound 7） exhibited the strongest activities in suppress- ing the production of NO, TNF-（x, and PGE2 in LPS-activated RAW264.7 cells and peritoneal macrophages （the ICso values=l-5 pmol/L）. This compound （1.25-20 pmol/L） dose-dependently suppressed the expression of the pro-inflammatory genes for iNOS, COX-2, TNF-a, and the cytokines IL-li3 and IL-6 at the level of transcription in LPS-activated RAW264.7 cells. 8-TQ （20 μmol/L） significantly sup-pressed the activation of NF-KB and its upstream signaling elements, including inhibitor of KB （IκBα）, IκBα kinase （IKK） and Akt in LPS- activated RAW264.7 cells. In in vivo experiments, oral administration of 20 and 40 mg/kg 8-TQ for 3 d significantly alleviated the signs of LPS-induced hepatitis and HCl/EtOH-induced gastritis, respectively, in ICR mice. Conclusion： 8-TQ （compound 7） exerts significant anti-inflammatory activity through the inhibition of the Akt/NF-KB pathway, thus may be developed as a novel anti-inflammatory drug.