Ephedrine attenuates LPS-induced M1 polarization of alveolar macrophages via the PKM2-mediated glycolysis.

IF 2.2 4区医学 Q3 TOXICOLOGY

Toxicology Research Pub Date : 2024-10-10 eCollection Date: 2024-10-01 DOI:10.1093/toxres/tfae166

Yijin Xiang, Zaifeng Jiang, Zhigang Yang, Shaomin Gong, Weiran Niu

{"title":"Ephedrine attenuates LPS-induced M1 polarization of alveolar macrophages via the PKM2-mediated glycolysis.","authors":"Yijin Xiang, Zaifeng Jiang, Zhigang Yang, Shaomin Gong, Weiran Niu","doi":"10.1093/toxres/tfae166","DOIUrl":null,"url":null,"abstract":"Background: Asthma is one of chronic inflammatory lung diseases in world. The important role of macrophage polarization and glycolysis in lung inflammation has attracted considerable attention. Ephedrine (EP) is a compound isolated from Ephedra and plays a regulatory role in inflammatory response, but its role in asthma and mechanism involved are not clear. Therefore, the purpose of this study was to investigate the molecular mechanism and effect of EP on lipopolysaccharide (LPS)-induced alveolar macrophage polarization and glycolysis.Methods: We investigated the expression of Tnf-a, Nos2, Il10, and Arg1 using RT-PCR, as well as PKM2 and LDHA protein expression with Western blot. A CCK-8 assay was performed to determine the viability of the cells. The extracellular acidification rate (ECAR), ATP and lactate level were detected using commercial kits.Results: The results revealed that EP alleviated LPS-induced NR8383 cell glycolysis and M1 polarization. Further studies found that EP enhanced the effect of 2-DG on NR8383 cell glycolysis and M1 polarization. More importantly, PKM2 inhibitor alleviated LPS-induced NR8383 cell glycolysis and M1 polarization. In addition, EP alleviated LPS-induced NR8383 cell glycolysis and M1 polarization by targeting PKM2.Conclusion: It is suggested that EP alleviates LPS-induced glycolysis and M1 polarization in NR8383 cells by regulating PKM2, thereby alleviating lung injury, suggesting the involvment of alveolar macrophage polarization and glycolysis in the role of EP in asthma.","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae166"},"PeriodicalIF":2.2000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465183/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/toxres/tfae166","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"TOXICOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Asthma is one of chronic inflammatory lung diseases in world. The important role of macrophage polarization and glycolysis in lung inflammation has attracted considerable attention. Ephedrine (EP) is a compound isolated from Ephedra and plays a regulatory role in inflammatory response, but its role in asthma and mechanism involved are not clear. Therefore, the purpose of this study was to investigate the molecular mechanism and effect of EP on lipopolysaccharide (LPS)-induced alveolar macrophage polarization and glycolysis.

Methods: We investigated the expression of Tnf-a, Nos2, Il10, and Arg1 using RT-PCR, as well as PKM2 and LDHA protein expression with Western blot. A CCK-8 assay was performed to determine the viability of the cells. The extracellular acidification rate (ECAR), ATP and lactate level were detected using commercial kits.

Results: The results revealed that EP alleviated LPS-induced NR8383 cell glycolysis and M1 polarization. Further studies found that EP enhanced the effect of 2-DG on NR8383 cell glycolysis and M1 polarization. More importantly, PKM2 inhibitor alleviated LPS-induced NR8383 cell glycolysis and M1 polarization. In addition, EP alleviated LPS-induced NR8383 cell glycolysis and M1 polarization by targeting PKM2.

Conclusion: It is suggested that EP alleviates LPS-induced glycolysis and M1 polarization in NR8383 cells by regulating PKM2, thereby alleviating lung injury, suggesting the involvment of alveolar macrophage polarization and glycolysis in the role of EP in asthma.

查看原文本刊更多论文

麻黄碱可通过 PKM2 介导的糖酵解减轻 LPS 诱导的肺泡巨噬细胞 M1 极化。

背景：哮喘是世界上慢性肺部炎症性疾病之一。巨噬细胞极化和糖酵解在肺部炎症中的重要作用引起了广泛关注。麻黄碱（Ephedrine，EP）是从麻黄中分离出来的一种化合物，在炎症反应中起调节作用，但其在哮喘中的作用及其机制尚不清楚。因此，本研究旨在探讨麻黄碱对脂多糖（LPS）诱导的肺泡巨噬细胞极化和糖酵解的分子机制和影响：方法：用RT-PCR检测Tnf-a、Nos2、Il10和Arg1的表达，用Western印迹检测PKM2和LDHA蛋白的表达。CCK-8试验测定了细胞的活力。使用商业试剂盒检测细胞外酸化率（ECAR）、ATP和乳酸水平：结果表明，EP 可减轻 LPS 诱导的 NR8383 细胞糖酵解和 M1 极化。进一步研究发现，EP 增强了 2-DG 对 NR8383 细胞糖酵解和 M1 极化的影响。更重要的是，PKM2 抑制剂减轻了 LPS 诱导的 NR8383 细胞糖酵解和 M1 极化。此外，EP通过靶向PKM2缓解了LPS诱导的NR8383细胞糖酵解和M1极化：结论：EP通过调节PKM2减轻LPS诱导的NR8383细胞糖酵解和M1极化，从而减轻肺损伤，表明EP在哮喘中的作用涉及肺泡巨噬细胞极化和糖酵解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Toxicology Research TOXICOLOGY-

CiteScore

3.60

自引率

0.00%

发文量

期刊介绍： A multi-disciplinary journal covering the best research in both fundamental and applied aspects of toxicology