{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T13:32:33Z","timestamp":1781530353804,"version":"3.54.1"},"reference-count":21,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013ATM pathway in driving macrophage inflammation.<\/jats:p>","DOI":"10.3390\/ijms25010169","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T01:19:42Z","timestamp":1703207982000},"page":"169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Antioxidants and azd0156 Rescue Inflammatory Response in Autophagy-Impaired Macrophages"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6344-9425","authenticated-orcid":false,"given":"Abdalla","family":"Elbialy","sequence":"first","affiliation":[{"name":"Division of Vascular Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, 1111 Highland Avenue, WIMR 5151, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Kitauchi","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, 1111 Highland Avenue, WIMR 5151, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5720-3939","authenticated-orcid":false,"given":"Dai","family":"Yamanouchi","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, 1111 Highland Avenue, WIMR 5151, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.immuni.2020.05.014","article-title":"Determinants of resident tissue macrophage identity and function","volume":"52","author":"Chakarov","year":"2020","journal-title":"Immunity"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1007\/s00018-019-03371-3","article-title":"Diversity of macrophage phenotypes and responses in atherosclerosis","volume":"77","author":"Jinnouchi","year":"2020","journal-title":"Cell. 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