title: TAK-242 attenuates acute cigarette smoke-induced pulmonary inflammation in mouse via the TLR4/NF-κB signaling pathway.
abstract: 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.
authors.affiliation: Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Tao
authors.affiliation: Department of General Surgery, West China Hospital, Sichuan University (Chengdu), 610041, PR China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Xion
authors.affiliation: Department of Emergency, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, PR China.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Emergency, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, PR China.
authors.forename: Yaowen
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, PR China. Electronic address: hesirong@cqmu.edu.cn.
authors.forename: Sirong
authors.initials: S
authors.lastname: He
mesh_terms: D000208:Acute Disease; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008168:Lung; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D011014:Pneumonia / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013449:Sulfonamides / Q000008:administration & dosage*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D016328:NF-kappa B; D013449:Sulfonamides; C493487:Tlr4 protein, mouse; D014028:Tobacco Smoke Pollution; D051197:Toll-Like Receptor 4; C507035:ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate
keywords: Inflammation; TAK-242; TLR4