Tranilast attenuates lipopolysaccharide‑induced lung injury via the CXCR4/JAK2/STAT3 signaling pathway

Lou,Yufeng; Huang,Zhenrong; Wu,Hui; Zhou,Yun

doi:10.3892/mmr.2022.12736

Tranilast attenuates lipopolysaccharide‑induced lung injury via the CXCR4/JAK2/STAT3 signaling pathway

Authors:
- Yufeng Lou
- Zhenrong Huang
- Hui Wu
- Yun Zhou
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Affiliations: Department of Emergency, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, Zhejiang 315020, P.R. China
Published online on: May 13, 2022 https://doi.org/10.3892/mmr.2022.12736
Article Number: 220
Copyright: © Lou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

It has been reported that the expression of C‑X‑C motif chemokine receptor 4 (CXCR4) is increased in patients with lung injury, while CXCR4 downregulation can improve sepsis‑induced lung injury. Previous studies have shown that tranilast can inhibit CXCR4 mRNA expression. Therefore, the present study aimed to investigate whether tranilast could protect against lipopolysaccharide (LPS)‑induced lung injury via the CXCR4/Janus kinase 2 (JAK2)/STAT3 signaling pathway. A Cell Counting Kit‑8 assay was performed to evaluate the effect of different concentrations of tranilast on the viability of LPS‑induced BEAS‑2B cells. The mRNA and protein expression levels of the inflammatory factors, TNFα, IL‑1β, IL‑6, cytochrome c oxidase subunit II and inducible nitric oxide synthase were detected using reverse transcription‑quantitative PCR and western blot analysis, respectively. In addition, the cell apoptosis rate and the expression levels of apoptosis‑related proteins were analyzed using a TUNEL staining assay and western blot analysis, respectively. The expression levels of the CXCR4/JAK2/STAT3 signaling pathway‑related proteins were also determined using western blot analysis. Furthermore, the effects of tranilast on cell viability, inflammation and apoptosis were also evaluated in LPS‑stimulated BEAS‑2B cells following CXCR4 overexpression, which were pre‑treated with tranilast. The results demonstrated that tranilast could alleviate LPS‑induced cell viability, the secretion of inflammatory cytokines and cell apoptosis. In addition, cell treatment with tranilast inhibited the expression of CXCR4/JAK2/STAT3 signaling‑related proteins in LPS‑induced BEAS‑2B cells. Following CXCR4 overexpression, the alleviating effect of tranilast on cell viability, inflammatory response and apoptosis was notably attenuated. Overall, the current study suggested that tranilast could attenuate LPS‑induced lung injury via the CXCR4/JAK2/STAT3 signaling pathway, suggesting that tranilast could be considered as a promising agent for treating sepsis‑induced acute lung injury.

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