Tomatidine activates autophagy to improve lung injury and inflammation in sepsis by inhibiting NF-κB and MAPK pathways.

IF 2.3 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Bo Xu, Min Huang, Hang Qi, Hongzhou Xu, Liang Cai
{"title":"Tomatidine activates autophagy to improve lung injury and inflammation in sepsis by inhibiting NF-κB and MAPK pathways.","authors":"Bo Xu, Min Huang, Hang Qi, Hongzhou Xu, Liang Cai","doi":"10.1007/s00438-024-02109-6","DOIUrl":null,"url":null,"abstract":"<p><p>Sepsis-induced acute lung injury (ALI) is a life-threatening medical condition with high mortality and morbidity. Autophagy is involved in the pathophysiological process of sepsis-induced ALI, including inflammation, which indicates that regulating autophagy may be beneficial for this disease. Tomatidine, a natural compound abundant in unripe tomatoes, has been reported to have anti-inflammatory, anti-tumorigenic, and lipid-lowering effects. However, the biological functions and mechanisms of tomatidine in sepsis-induced ALI remain unknown. The principal objective of this study was to investigate the effect of tomatidine on sepsis-induced ALI. Cecal ligation and puncture (CLP) was used to induce septic lung injury in mice, and 10 mg/kg tomatidine was intraperitoneally injected into mice 2 h after the operation. The results of hematoxylin and eosin staining and assessment of lung edema and total protein levels in bronchoalveolar lavage fluid (BALF) demonstrated that tomatidine alleviated CLP-induced severe lung injuries such as hemorrhage, infiltration of inflammatory cells, and interstitial and alveolar edema in mice. Additionally, the levels of proinflammatory cytokines in BALF and lung tissues were measured by enzyme-linked immunosorbent assay (ELISA), and the results showed that tomatidine inhibited CLP-induced inflammatory damage to lungs. Moreover, the results of western blotting showed that tomatidine promoted autophagy during CLP-induced ALI. Mechanistically, immunofluorescence staining and western blotting were used to measure the protein levels of TLR4, phosphorylated NF-κB, phosphorylated IκBα, and phosphorylated MAPKs, showing that tomatidine inactivated NF-κB and MAPK signaling in lung tissues of CLP-induced ALI mice. In conclusion, tomatidine exerts protective effects against sepsis-induced severe damage to the lungs by inhibiting inflammation and activating autophagy in CLP-treated mice through inactivating the NF-κB and MAPK pathways, which may be an effective candidate for treating septic ALI.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Genetics and Genomics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s00438-024-02109-6","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Sepsis-induced acute lung injury (ALI) is a life-threatening medical condition with high mortality and morbidity. Autophagy is involved in the pathophysiological process of sepsis-induced ALI, including inflammation, which indicates that regulating autophagy may be beneficial for this disease. Tomatidine, a natural compound abundant in unripe tomatoes, has been reported to have anti-inflammatory, anti-tumorigenic, and lipid-lowering effects. However, the biological functions and mechanisms of tomatidine in sepsis-induced ALI remain unknown. The principal objective of this study was to investigate the effect of tomatidine on sepsis-induced ALI. Cecal ligation and puncture (CLP) was used to induce septic lung injury in mice, and 10 mg/kg tomatidine was intraperitoneally injected into mice 2 h after the operation. The results of hematoxylin and eosin staining and assessment of lung edema and total protein levels in bronchoalveolar lavage fluid (BALF) demonstrated that tomatidine alleviated CLP-induced severe lung injuries such as hemorrhage, infiltration of inflammatory cells, and interstitial and alveolar edema in mice. Additionally, the levels of proinflammatory cytokines in BALF and lung tissues were measured by enzyme-linked immunosorbent assay (ELISA), and the results showed that tomatidine inhibited CLP-induced inflammatory damage to lungs. Moreover, the results of western blotting showed that tomatidine promoted autophagy during CLP-induced ALI. Mechanistically, immunofluorescence staining and western blotting were used to measure the protein levels of TLR4, phosphorylated NF-κB, phosphorylated IκBα, and phosphorylated MAPKs, showing that tomatidine inactivated NF-κB and MAPK signaling in lung tissues of CLP-induced ALI mice. In conclusion, tomatidine exerts protective effects against sepsis-induced severe damage to the lungs by inhibiting inflammation and activating autophagy in CLP-treated mice through inactivating the NF-κB and MAPK pathways, which may be an effective candidate for treating septic ALI.

Abstract Image

托马替丁通过抑制 NF-κB 和 MAPK 通路激活自噬,从而改善败血症的肺损伤和炎症。
败血症诱发的急性肺损伤(ALI)是一种危及生命的疾病,死亡率和发病率都很高。自噬参与了败血症诱发的急性肺损伤的病理生理过程,包括炎症,这表明调节自噬可能对这种疾病有益。据报道,番茄碱是一种天然化合物,在未成熟的番茄中含量丰富,具有抗炎、抗肿瘤和降血脂的作用。然而,番茄碱在败血症诱发的 ALI 中的生物功能和机制仍不清楚。本研究的主要目的是探讨托马替丁对脓毒症诱发的 ALI 的影响。采用盲肠结扎术(CLP)诱导小鼠脓毒性肺损伤,术后2小时腹腔注射10 mg/kg托马替丁。苏木精和伊红染色以及支气管肺泡灌洗液(BALF)中肺水肿和总蛋白水平的评估结果表明,托马替丁可减轻CLP诱导的小鼠严重肺损伤,如出血、炎症细胞浸润、肺间质和肺泡水肿。此外,用酶联免疫吸附试验(ELISA)检测了 BALF 和肺组织中促炎细胞因子的水平,结果表明托马替丁抑制了 CLP 引起的肺部炎症损伤。此外,Western 印迹的结果表明,在 CLP 诱导的 ALI 中,托马替丁促进了自噬。从机理上讲,免疫荧光染色和免疫印迹法检测了TLR4、磷酸化NF-κB、磷酸化IκBα和磷酸化MAPKs的蛋白水平,结果表明,在CLP诱导的ALI小鼠肺组织中,托马替丁灭活了NF-κB和MAPK信号转导。总之,托马替丁通过灭活NF-κB和MAPK通路,抑制CLP诱导的小鼠肺部炎症并激活自噬,从而对脓毒症诱导的肺部严重损伤起到保护作用,可能是治疗脓毒症ALI的有效候选药物。
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
Molecular Genetics and Genomics
Molecular Genetics and Genomics 生物-生化与分子生物学
CiteScore
5.10
自引率
3.20%
发文量
134
审稿时长
1 months
期刊介绍: Molecular Genetics and Genomics (MGG) publishes peer-reviewed articles covering all areas of genetics and genomics. Any approach to the study of genes and genomes is considered, be it experimental, theoretical or synthetic. MGG publishes research on all organisms that is of broad interest to those working in the fields of genetics, genomics, biology, medicine and biotechnology. The journal investigates a broad range of topics, including these from recent issues: mechanisms for extending longevity in a variety of organisms; screening of yeast metal homeostasis genes involved in mitochondrial functions; molecular mapping of cultivar-specific avirulence genes in the rice blast fungus and more.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信