title: JNK inhibitor SP600125 protects against lipopolysaccharide-induced acute lung injury via upregulation of claudin-4.
abstract: Althoughin vitrostudies have previously demonstrated that mitogen-activated protein kinases are important for the activation of transcription factors and the regulation of proinflammatory mediators, the function of c-Jun NH2-terminal kinase (JNK) in acute lung injury (ALI) remains to be fully elucidated. The present study aimed to investigate the effect of the JNK selective inhibitor SP600125 on lipopolysaccharide (LPS)-induced ALI. Pulmonary edema, the expression of inflammatory cytokines and pathological alterations were found to be significantly attenuated in LPS-induced ALI following treatment with SP600125in vivo. In vitro, it was demonstrated that SP600125 administration significantly improved A549 cell viability in a dose-dependent manner using the Cell Counting kit-8 and the 5-ethynyl-2'-deoxyuridine incorporation assay. Furthermore, flow cytometric analysis demonstrated that the apoptotic rate was significantly reduced in a concentration-dependent manner following SP600125 injection. At the molecular level, SP600125 treatment dose-dependently inhibited JNK activation and upregulated claudin-4 expressionin vivoandin vitro. In combination, the results from the present study indicated that the JNK inhibitor SP600125 protected against LPS-induced ALIin vivoandin vitro,possibly by upregulating the expression of claudin-4.
authors.affiliation: Department of Emergency, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Yueliang
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Emergency, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Meiqi
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Emergency, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Emergency, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Emergency, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Emergency, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Cai
keywords: JNK inhibitor; acute lung injury; claudin-4; lipopolysaccharide