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

IF 2.9 4区 生物学 Q2 BIOPHYSICS
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.

埃索美拉唑介导内质网应激对脓毒性肺损伤的抗炎作用。
以过度活跃的肺部炎症为特征的急性肺损伤是脓毒症常见而严重的并发症。埃索美拉唑(Esomeprazole, ESO)是一种有效的质子泵抑制剂(PPI),已被证明是治疗高浓度脓毒症的一种有前景的抗炎药,但其在脓毒症诱导的肺损伤中的疗效尚未被探索。本研究旨在探讨ESO在脓毒性肺损伤中的作用及其可能机制。在构建盲肠结扎和穿刺(CLP)脓毒症模型之前,用ESO预处理小鼠。将MH-S肺巨噬细胞暴露于脂多糖(LPS)诱导炎症损伤。采用H&E染色、乳酸脱氢酶(LDH)测定和肺干湿重(W/D)比检测肺损伤程度。采用酶联免疫吸附法(ELISA)和免疫印迹法(Western blotting)检测炎症因子水平。计数炎症细胞的数量。巨噬细胞标记物免疫组化染色测定巨噬细胞分布。Western blotting还检测了内质网应激(ERS)和NLR家族pyrin domain containing 3 (NLRP3)炎性小体相关蛋白的表达。CCK-8法检测细胞活力。ESO浓度依赖性地减轻脓毒症小鼠肺组织病理损伤,降低LDH活性、肺W/D比,降低肺组织炎症细胞计数和F4/80表达。此外,ESO在体外和体内均抑制炎症反应、NLRP3炎性小体激活和失活活化转录因子6 (ATF6)- ccaat增强子结合蛋白同源蛋白(CHOP)介导的ERS信号。ATF6过表达部分逆转了ESO对lps诱导的MH-S细胞NLRP3炎性小体和炎性细胞因子水平的影响。无论如何,ESO可能抑制ATF6/CHOP通路,以保护脓毒性肺损伤的炎症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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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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