JNK inhibitor SP600125 protects against lipopolysaccharide‑induced acute lung injury via upregulation of claudin‑4

Zheng,Yueliang; Zhang,Meiqi; Zhao,Yiming; Chen,Jie; Li,Bing; Cai,Wenwei

doi:10.3892/etm.2014.1684

JNK inhibitor SP600125 protects against lipopolysaccharide‑induced acute lung injury via upregulation of claudin‑4

Authors:
- Yueliang Zheng
- Meiqi Zhang
- Yiming Zhao
- Jie Chen
- Bing Li
- Wenwei Cai
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Affiliations: Department of Emergency, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China
Published online on: April 14, 2014 https://doi.org/10.3892/etm.2014.1684
Pages: 153-158

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Abstract

Although in vitro studies 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 SP600125 in 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 expression in vivo and in vitro. In combination, the results from the present study indicated that the JNK inhibitor SP600125 protected against LPS‑induced ALI in vivo and in vitro, possibly by upregulating the expression of claudin‑4.

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