Wang Dan, Tao Kun, Xion Junjie, Xu Shuyun, Jiang Yaowen, Chen Quan, He Sirong
Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, PR China.
Department of General Surgery, West China Hospital, Sichuan University (Chengdu), 610041, PR China.
Biochem Biophys Res Commun. 2016 Apr 8;472(3):508-15. doi: 10.1016/j.bbrc.2016.03.001. Epub 2016 Mar 2.
The present study determined the effect of TAK-242 on attenuating acute cigarette smoke induced pulmonary inflammation and attempted to dissect its underlying mechanisms of action. When administered to the C57BL/6J mice after a 3 days period of cigarettes exposure,TAK-242 significantly decreased the accumulation of macrophages, neutrophils, lymphocytes and DCs, and upregulation of IL-6, IL-8 and TNF-α in BAL fluid and lungs in a dose-dependent manner, except MCP-1, IL-1β and IFN-γ, which demonstrated that TAK-242 inhibits release of various inflammatory mediators induced by cigarette smoke. TAK-242 also significantly suppressed the expression of TLR4, MyD88 and the activation of NF-κB in lungs, suggesting that TAK-242-mediated inhibition occurred largely through the TLR4/NF-κB signal pathway. Our results support TAK-242 as a potent therapeutic agent in the treatment of cigarette smoke induced-pulmonary inflammation, and warrants further pharmaceutical investigation.
本研究确定了TAK - 242对减轻急性香烟烟雾诱导的肺部炎症的作用，并试图剖析其潜在的作用机制。在对C57BL / 6J小鼠进行3天香烟暴露后给予TAK - 242，TAK - 242以剂量依赖的方式显著降低了BAL液和肺中巨噬细胞、中性粒细胞、淋巴细胞和DC的积聚，以及IL - 6、IL - 8和TNF -α的上调，但MCP - 1、IL - 1β和IFN -γ除外，这表明TAK - 242抑制香烟烟雾诱导的各种炎症介质的释放。TAK - 242还显著抑制肺中TLR4、MyD88的表达以及NF -κB的激活，表明TAK - 242介导的抑制作用主要通过TLR4 / NF -κB信号通路发生。我们的结果支持TAK - 242作为治疗香烟烟雾诱导的肺部炎症的有效治疗剂，并值得进一步的药物研究。
