Anti-inflammatory effects of Esomeprazole in septic lung injury by mediating endoplasmic reticulum stress.

IF 2.9 4区 生物学 Q2 BIOPHYSICS Journal of Bioenergetics and Biomembranes Pub Date : 2025-03-12 DOI:10.1007/s10863-025-10055-0
Peng Wang, Hui Li, Wencheng Wu
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引用次数: 0

Abstract

Acute lung injury characterized by overactive pulmonary inflammation is a common and serious complication of sepsis. Esomeprazole (ESO), a potent proton pump inhibitor (PPI), has been demonstrated as a promising anti-inflammatory agent in treating sepsis at high concentrations, the efficacy of which in sepsis-induced lung injury has not been explored. This research aimed to investigate the role of ESO in septic lung injury and the potential mechanism. The mice were pretreated by ESO prior to the construction of cecal ligation and puncture (CLP) sepsis model. MH-S lung macrophages were exposed to lipopolysaccharide (LPS) to induce inflammatory injury. The severity of lung damage was detected by H&E staining, measurement of lactic dehydrogenase (LDH) and lung wet/dry weight (W/D) ratio. The levels of inflammatory cytokines were detected by ELISA and Western blotting. The number of inflammatory cells was counted. Macrophage distribution was measured by immunohistochemical staining of macrophage markers. Western blotting also determined the expression of endoplasmic reticulum stress (ERS) and NLR family pyrin domain containing 3 (NLRP3) inflammasome-related proteins. CCK-8 method was used to detect cell viability. ESO concentration-dependently mitigated the pathological damage of lung tissues, reduced LDH activity, lung W/D ratio, decreased inflammatory cell counts and F4/80 expression in the lung tissues of sepsis mice. Besides, ESO suppressed inflammatory response, NLRP3 inflammasome activation and inactivated activating transcription factor 6 (ATF6)-CCAAT-enhancer-binding protein homologous protein (CHOP)-mediated ERS signaling both in vitro and in vivo. ATF6 overexpression partially reversed the impacts of ESO on NLRP3 inflammasome and the levels of inflammatory cytokines in LPS-induced MH-S cells. Anyway, ESO may inhibit ATF6/CHOP pathway to protect against inflammation in septic lung injury.

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来源期刊
CiteScore
6.00
自引率
0.00%
发文量
22
审稿时长
6-12 weeks
期刊介绍: The Journal of Bioenergetics and Biomembranes is an international journal devoted to the publication of original research that contributes to fundamental knowledge in the areas of bioenergetics, biomembranes, and transport, including oxidative phosphorylation, photosynthesis, muscle contraction, as well as cellular and systemic metabolism. The timely research in this international journal benefits biophysicists, membrane biologists, cell biologists, biochemists, molecular biologists, physiologists, endocrinologists, and bio-organic chemists.
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