{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T11:57:14Z","timestamp":1772452634318,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T00:00:00Z","timestamp":1677110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["GRK 2336 TP5-Project ID 321115009"],"award-info":[{"award-number":["GRK 2336 TP5-Project ID 321115009"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["SFB 1039\/3 B6\u2013Project ID 204083920"],"award-info":[{"award-number":["SFB 1039\/3 B6\u2013Project ID 204083920"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["EXC 2026, Project ID: 390649896"],"award-info":[{"award-number":["EXC 2026, Project ID: 390649896"]}]},{"name":"China Scholarship Council","award":["GRK 2336 TP5-Project ID 321115009"],"award-info":[{"award-number":["GRK 2336 TP5-Project ID 321115009"]}]},{"name":"China Scholarship Council","award":["SFB 1039\/3 B6\u2013Project ID 204083920"],"award-info":[{"award-number":["SFB 1039\/3 B6\u2013Project ID 204083920"]}]},{"name":"China Scholarship Council","award":["EXC 2026, Project ID: 390649896"],"award-info":[{"award-number":["EXC 2026, Project ID: 390649896"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Macrophages are highly plastic immune cells that can be reprogrammed to pro-inflammatory or pro-resolving phenotypes by different stimuli and cell microenvironments. This study set out to assess gene expression changes associated with the transforming growth factor (TGF)-\u03b2-induced polarization of classically activated macrophages into a pro-resolving phenotype. Genes upregulated by TGF-\u03b2 included Pparg; which encodes the transcription factor peroxisome proliferator-activated receptor (PPAR)-\u03b3, and several PPAR-\u03b3 target genes. TGF-\u03b2 also increased PPAR-\u03b3 protein expression via activation of the Alk5 receptor to increase PPAR-\u03b3 activity. Preventing PPAR-\u03b3 activation markedly impaired macrophage phagocytosis. TGF-\u03b2 repolarized macrophages from animals lacking the soluble epoxide hydrolase (sEH); however, it responded differently and expressed lower levels of PPAR-\u03b3-regulated genes. The sEH substrate 11,12-epoxyeicosatrienoic acid (EET), which was previously reported to activate PPAR-\u03b3, was elevated in cells from sEH\u2212\/\u2212 mice. However, 11,12-EET prevented the TGF-\u03b2-induced increase in PPAR-\u03b3 levels and activity, at least partly by promoting proteasomal degradation of the transcription factor. This mechanism is likely to underlie the impact of 11,12-EET on macrophage activation and the resolution of inflammation.<\/jats:p>","DOI":"10.3390\/cells12050700","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T03:25:56Z","timestamp":1677122756000},"page":"700","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["11,12-EET Regulates PPAR-\u03b3 Expression to Modulate TGF-\u03b2-Mediated Macrophage Polarization"],"prefix":"10.3390","volume":"12","author":[{"given":"Xiaoming","family":"Li","sequence":"first","affiliation":[{"name":"Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, 60596 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Kempf","sequence":"additional","affiliation":[{"name":"Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, 60596 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Heart and Lung Research, Bioinformatics and Deep Sequencing Platform, 61231 Bad Nauheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiong","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, 60596 Frankfurt am Main, Germany"},{"name":"Department of Histology and Embryology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1881-3635","authenticated-orcid":false,"given":"Ingrid","family":"Fleming","sequence":"additional","affiliation":[{"name":"Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, 60596 Frankfurt am Main, Germany"},{"name":"German Center of Cardiovascular Research (DZHK), Partner Site RheinMain, 60596 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nrd.2016.39","article-title":"Resolution of inflammation: A new therapeutic frontier","volume":"15","author":"Fullerton","year":"2016","journal-title":"Nat. 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