{"title":"臭氧诱发肺部炎症损伤的脂肪酸代谢:证据、机制和预防","authors":"Mengyuan Li, Xiangbing Kong, Xiaotong Jian, Yacong Bo, Xinyi Miao, Huaiyong Chen, Pingping Shang, Xiaolei Zhou, Ling Wang, Qiao Zhang, Qihong Deng, Yuan Xue, Feifei Feng","doi":"10.1016/j.scitotenv.2024.173222","DOIUrl":null,"url":null,"abstract":"<p><p>Ozone (O<sub>3</sub>) is a major air pollutant that directly threatens the respiratory system, lung fatty acid metabolism disorder is an important molecular event in pulmonary inflammatory diseases. Liver kinase B1 (LKB1) and nucleotide-binding domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome not only regulate inflammation, but also have close relationship with fatty acid metabolism. However, the role and mechanism of LKB1 and NLRP3 inflammasome in lung fatty acid metabolism, which may contribute to ozone-induced lung inflammation, remain unclear, and effective strategy for preventing O<sub>3</sub>-induced pulmonary inflammatory injury is lacking. To explore these, mice were exposed to 1.00 ppm O<sub>3</sub> (3 h/d, 5 days), and pulmonary inflammation was determined by airway hyperresponsiveness, histopathological examination, total cells and cytokines in bronchoalveolar lavage fluid (BALF). Targeted fatty acids metabolomics was used to detect medium and long fatty acid in lung tissue. Then, using LKB1-overexpressing adenovirus and NLRP3 knockout (NLRP3-/-) mice to explore the mechanism of O<sub>3</sub>-induced lung fatty acid metabolism disorder. Results demonstrated that O<sub>3</sub> exposure caused pulmonary inflammatory injury and lung medium and long chain fatty acids metabolism disorder, especially decreased dihomo-γ-linolenic acid (DGLA). Meanwhile, LKB1 expression was decreased, and NLRP3 inflammasome was activated in lung of mice after O<sub>3</sub> exposure. Additionally, LKB1 overexpression alleviated O<sub>3</sub>-induced lung inflammation and inhibited the activation of NLRP3 inflammasome. And we found that pulmonary fatty acid metabolism disorder was ameliorated of NLRP3 -/- mice compared with those in wide type mice after O<sub>3</sub> exposure. Furthermore, administrating DGLA intratracheally prior to O<sub>3</sub> exposure significantly attenuated O<sub>3</sub>-induced pulmonary inflammatory injury. Taken together, these findings suggest that fatty acids metabolism disorder is involved in O<sub>3</sub>-induced pulmonary inflammation, which is regulated by LKB1-mediated NLRP3 pathway, DGLA supplement could be a useful preventive strategy to ameliorate ozone-associated lung inflammatory injury.</p>","PeriodicalId":422,"journal":{"name":"Science of the Total Environment","volume":null,"pages":null},"PeriodicalIF":8.2000,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Fatty acids metabolism in ozone-induced pulmonary inflammatory injury: Evidence, mechanism and prevention.\",\"authors\":\"Mengyuan Li, Xiangbing Kong, Xiaotong Jian, Yacong Bo, Xinyi Miao, Huaiyong Chen, Pingping Shang, Xiaolei Zhou, Ling Wang, Qiao Zhang, Qihong Deng, Yuan Xue, Feifei Feng\",\"doi\":\"10.1016/j.scitotenv.2024.173222\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Ozone (O<sub>3</sub>) is a major air pollutant that directly threatens the respiratory system, lung fatty acid metabolism disorder is an important molecular event in pulmonary inflammatory diseases. Liver kinase B1 (LKB1) and nucleotide-binding domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome not only regulate inflammation, but also have close relationship with fatty acid metabolism. However, the role and mechanism of LKB1 and NLRP3 inflammasome in lung fatty acid metabolism, which may contribute to ozone-induced lung inflammation, remain unclear, and effective strategy for preventing O<sub>3</sub>-induced pulmonary inflammatory injury is lacking. To explore these, mice were exposed to 1.00 ppm O<sub>3</sub> (3 h/d, 5 days), and pulmonary inflammation was determined by airway hyperresponsiveness, histopathological examination, total cells and cytokines in bronchoalveolar lavage fluid (BALF). Targeted fatty acids metabolomics was used to detect medium and long fatty acid in lung tissue. Then, using LKB1-overexpressing adenovirus and NLRP3 knockout (NLRP3-/-) mice to explore the mechanism of O<sub>3</sub>-induced lung fatty acid metabolism disorder. Results demonstrated that O<sub>3</sub> exposure caused pulmonary inflammatory injury and lung medium and long chain fatty acids metabolism disorder, especially decreased dihomo-γ-linolenic acid (DGLA). Meanwhile, LKB1 expression was decreased, and NLRP3 inflammasome was activated in lung of mice after O<sub>3</sub> exposure. Additionally, LKB1 overexpression alleviated O<sub>3</sub>-induced lung inflammation and inhibited the activation of NLRP3 inflammasome. And we found that pulmonary fatty acid metabolism disorder was ameliorated of NLRP3 -/- mice compared with those in wide type mice after O<sub>3</sub> exposure. Furthermore, administrating DGLA intratracheally prior to O<sub>3</sub> exposure significantly attenuated O<sub>3</sub>-induced pulmonary inflammatory injury. Taken together, these findings suggest that fatty acids metabolism disorder is involved in O<sub>3</sub>-induced pulmonary inflammation, which is regulated by LKB1-mediated NLRP3 pathway, DGLA supplement could be a useful preventive strategy to ameliorate ozone-associated lung inflammatory injury.</p>\",\"PeriodicalId\":422,\"journal\":{\"name\":\"Science of the Total Environment\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.2000,\"publicationDate\":\"2024-07-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Science of the Total Environment\",\"FirstCategoryId\":\"93\",\"ListUrlMain\":\"https://doi.org/10.1016/j.scitotenv.2024.173222\",\"RegionNum\":1,\"RegionCategory\":\"环境科学与生态学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/13 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ENVIRONMENTAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science of the Total Environment","FirstCategoryId":"93","ListUrlMain":"https://doi.org/10.1016/j.scitotenv.2024.173222","RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/13 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
Fatty acids metabolism in ozone-induced pulmonary inflammatory injury: Evidence, mechanism and prevention.
Ozone (O3) is a major air pollutant that directly threatens the respiratory system, lung fatty acid metabolism disorder is an important molecular event in pulmonary inflammatory diseases. Liver kinase B1 (LKB1) and nucleotide-binding domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome not only regulate inflammation, but also have close relationship with fatty acid metabolism. However, the role and mechanism of LKB1 and NLRP3 inflammasome in lung fatty acid metabolism, which may contribute to ozone-induced lung inflammation, remain unclear, and effective strategy for preventing O3-induced pulmonary inflammatory injury is lacking. To explore these, mice were exposed to 1.00 ppm O3 (3 h/d, 5 days), and pulmonary inflammation was determined by airway hyperresponsiveness, histopathological examination, total cells and cytokines in bronchoalveolar lavage fluid (BALF). Targeted fatty acids metabolomics was used to detect medium and long fatty acid in lung tissue. Then, using LKB1-overexpressing adenovirus and NLRP3 knockout (NLRP3-/-) mice to explore the mechanism of O3-induced lung fatty acid metabolism disorder. Results demonstrated that O3 exposure caused pulmonary inflammatory injury and lung medium and long chain fatty acids metabolism disorder, especially decreased dihomo-γ-linolenic acid (DGLA). Meanwhile, LKB1 expression was decreased, and NLRP3 inflammasome was activated in lung of mice after O3 exposure. Additionally, LKB1 overexpression alleviated O3-induced lung inflammation and inhibited the activation of NLRP3 inflammasome. And we found that pulmonary fatty acid metabolism disorder was ameliorated of NLRP3 -/- mice compared with those in wide type mice after O3 exposure. Furthermore, administrating DGLA intratracheally prior to O3 exposure significantly attenuated O3-induced pulmonary inflammatory injury. Taken together, these findings suggest that fatty acids metabolism disorder is involved in O3-induced pulmonary inflammation, which is regulated by LKB1-mediated NLRP3 pathway, DGLA supplement could be a useful preventive strategy to ameliorate ozone-associated lung inflammatory injury.
期刊介绍:
The Science of the Total Environment is an international journal dedicated to scientific research on the environment and its interaction with humanity. It covers a wide range of disciplines and seeks to publish innovative, hypothesis-driven, and impactful research that explores the entire environment, including the atmosphere, lithosphere, hydrosphere, biosphere, and anthroposphere.
The journal's updated Aims & Scope emphasizes the importance of interdisciplinary environmental research with broad impact. Priority is given to studies that advance fundamental understanding and explore the interconnectedness of multiple environmental spheres. Field studies are preferred, while laboratory experiments must demonstrate significant methodological advancements or mechanistic insights with direct relevance to the environment.