{"title":"抗氧化剂和azd0156能挽救自噬功能受损的巨噬细胞的炎症反应","authors":"Abdalla Elbialy, Mai Kitauchi, Dai Yamanouchi","doi":"10.3390/ijms25010169","DOIUrl":null,"url":null,"abstract":"Autophagy is a lysosomal degradation system that eliminates and recycles damaged intracellular organelles and proteins. Inflammatory macrophages play a critical role in the development of various age-related inflammatory illnesses such as abdominal aortic aneurysm, atherosclerosis, and rheumatoid arthritis; therefore, identifying the mechanisms that cause macrophage inflammation is crucial for a better understanding of and developing therapeutics for inflammatory diseases. Previous research has linked autophagy to macrophage inflammation; Atg16L1-deficient macrophages increase IL-1 and IL-18 production via inflammasome activation. In this study, however, we show an alternative pathway of macrophage inflammation in an autophagy-deficient environment. We found that inhibiting autophagy in THP1 macrophages progressively increased the expression of p65-mediated inflammatory genes. This effect was reversed by treatment with antioxidants or azd0156, an ataxia telangiectasia mutated (ATM) inhibitor. In addition, our results showed that M1 macrophages inhibit autophagy and induce DNA damage, whereas M2 macrophages activate autophagy and reduce DNA damage. Importantly, the chemical activation of autophagy or ATM inhibition during M1 polarization reduced the M1 phenotype and inflammation, whereas inhibiting autophagy during M2 polarization also reduced the M2 phenotype. Thus, our findings highlight the importance of the autophagy–ATM pathway in driving macrophage inflammation.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":"85 7","pages":""},"PeriodicalIF":4.9000,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Antioxidants and azd0156 Rescue Inflammatory Response in Autophagy-Impaired Macrophages\",\"authors\":\"Abdalla Elbialy, Mai Kitauchi, Dai Yamanouchi\",\"doi\":\"10.3390/ijms25010169\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Autophagy is a lysosomal degradation system that eliminates and recycles damaged intracellular organelles and proteins. Inflammatory macrophages play a critical role in the development of various age-related inflammatory illnesses such as abdominal aortic aneurysm, atherosclerosis, and rheumatoid arthritis; therefore, identifying the mechanisms that cause macrophage inflammation is crucial for a better understanding of and developing therapeutics for inflammatory diseases. Previous research has linked autophagy to macrophage inflammation; Atg16L1-deficient macrophages increase IL-1 and IL-18 production via inflammasome activation. In this study, however, we show an alternative pathway of macrophage inflammation in an autophagy-deficient environment. We found that inhibiting autophagy in THP1 macrophages progressively increased the expression of p65-mediated inflammatory genes. This effect was reversed by treatment with antioxidants or azd0156, an ataxia telangiectasia mutated (ATM) inhibitor. In addition, our results showed that M1 macrophages inhibit autophagy and induce DNA damage, whereas M2 macrophages activate autophagy and reduce DNA damage. Importantly, the chemical activation of autophagy or ATM inhibition during M1 polarization reduced the M1 phenotype and inflammation, whereas inhibiting autophagy during M2 polarization also reduced the M2 phenotype. Thus, our findings highlight the importance of the autophagy–ATM pathway in driving macrophage inflammation.\",\"PeriodicalId\":49179,\"journal\":{\"name\":\"International Journal of Molecular Sciences\",\"volume\":\"85 7\",\"pages\":\"\"},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2023-12-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Molecular Sciences\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.3390/ijms25010169\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Molecular Sciences","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3390/ijms25010169","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Antioxidants and azd0156 Rescue Inflammatory Response in Autophagy-Impaired Macrophages
Autophagy is a lysosomal degradation system that eliminates and recycles damaged intracellular organelles and proteins. Inflammatory macrophages play a critical role in the development of various age-related inflammatory illnesses such as abdominal aortic aneurysm, atherosclerosis, and rheumatoid arthritis; therefore, identifying the mechanisms that cause macrophage inflammation is crucial for a better understanding of and developing therapeutics for inflammatory diseases. Previous research has linked autophagy to macrophage inflammation; Atg16L1-deficient macrophages increase IL-1 and IL-18 production via inflammasome activation. In this study, however, we show an alternative pathway of macrophage inflammation in an autophagy-deficient environment. We found that inhibiting autophagy in THP1 macrophages progressively increased the expression of p65-mediated inflammatory genes. This effect was reversed by treatment with antioxidants or azd0156, an ataxia telangiectasia mutated (ATM) inhibitor. In addition, our results showed that M1 macrophages inhibit autophagy and induce DNA damage, whereas M2 macrophages activate autophagy and reduce DNA damage. Importantly, the chemical activation of autophagy or ATM inhibition during M1 polarization reduced the M1 phenotype and inflammation, whereas inhibiting autophagy during M2 polarization also reduced the M2 phenotype. Thus, our findings highlight the importance of the autophagy–ATM pathway in driving macrophage inflammation.
期刊介绍:
The International Journal of Molecular Sciences (ISSN 1422-0067) provides an advanced forum for chemistry, molecular physics (chemical physics and physical chemistry) and molecular biology. It publishes research articles, reviews, communications and short notes. Our aim is to encourage scientists to publish their theoretical and experimental results in as much detail as possible. Therefore, there is no restriction on the length of the papers or the number of electronics supplementary files. For articles with computational results, the full experimental details must be provided so that the results can be reproduced. Electronic files regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material (including animated pictures, videos, interactive Excel sheets, software executables and others).