TAK-242 attenuates acute cigarette smoke-induced pulmonary inflammation in mouse via the TLR4/NF-κB signaling pathway

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-alpha in BAL fluid and lungs in a dose-dependent manner, except MCP-1, IL-1 beta and IFN-gamma, 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-kappa B in lungs, suggesting that TAK-242-mediated inhibition occurred largely through the TLR4/NF-kappa B 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. (C) 2016 Elsevier Inc. All rights reserved.