{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:38:24Z","timestamp":1792165104628,"version":"4.4.0"},"reference-count":62,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1A5A2019210, 2020R1A2B5B02001686"],"award-info":[{"award-number":["2020R1A5A2019210, 2020R1A2B5B02001686"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The signal transducer and activator of transcription 6 (STAT6) transcription factor promotes activation of the peroxisome proliferator-activated receptor gamma (PPAR\u03b3) pathway in macrophages. Little is known about the effect of proximal signal transduction leading to PPAR\u03b3 activation for the resolution of acute inflammation. Here, we studied the role of STAT6 signaling in PPAR\u03b3 activation and the resolution of acute sterile inflammation in a murine model of zymosan-induced peritonitis. First, we showed that STAT6 is aberrantly activated in peritoneal macrophages after zymosan injection. Utilizing STAT6\u2212\/\u2212 and wild-type (WT) mice, we found that STAT6 deficiency further enhanced zymosan-induced proinflammatory cytokines, such as tumor necrosis factor-\u03b1, interleukin (IL)-6, and macrophage inflammatory protein-2 in peritoneal lavage fluid (PLF) and serum, neutrophil numbers and total protein amount in PLF, but reduced proresolving molecules, such as IL-10 and hepatocyte growth factor, in PLF. The peritoneal macrophages and spleens of STAT6\u2212\/\u2212 mice exhibited lower mRNA and protein levels of PPAR\u03b3 and its target molecules over the course of inflammation than those of WT mice. The deficiency of STAT6 was shown to impair efferocytosis by peritoneal macrophages. Taken together, these results suggest that enhanced STAT6 signaling results in PPAR\u03b3-mediated macrophage programming, contributing to increased efferocytosis and inflammation resolution.<\/jats:p>","DOI":"10.3390\/cells10030501","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T09:47:20Z","timestamp":1614332840000},"page":"501","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["STAT6 Signaling Mediates PPAR\u03b3 Activation and Resolution of Acute Sterile Inflammation in Mice"],"prefix":"10.3390","volume":"10","author":[{"given":"Ye-JI","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Physiology, College of Medicine, Ewha Womans University, Seoul 07804, Korea"},{"name":"Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07804, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Min","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Ewha Womans University, Seoul 07804, Korea"},{"name":"Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07804, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1084-0367","authenticated-orcid":false,"given":"Young-Ho","family":"Ahn","sequence":"additional","affiliation":[{"name":"Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07804, Korea"},{"name":"Department of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul 07804, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Ha","family":"Choi","sequence":"additional","affiliation":[{"name":"Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07804, Korea"},{"name":"Department of Pharmacology, College of Medicine, Ewha Womans University, Seoul 07804, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youn-Hee","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Ewha Womans University, Seoul 07804, Korea"},{"name":"Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07804, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihee Lee","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Ewha Womans University, Seoul 07804, Korea"},{"name":"Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07804, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.2337\/diabetes.53.2007.S43","article-title":"The biology of peroxisome proliferator-activated receptors: Relationship with lipid metabolism and insulin sensitivity","volume":"53","author":"Ferre","year":"2004","journal-title":"Diabetes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6712","DOI":"10.1073\/pnas.1031789100","article-title":"PPARgamma and PPARdelta negatively regulate specific subsets of lipopolysaccharide and IFN-gamma target genes in macrophages","volume":"100","author":"Welch","year":"2003","journal-title":"Proc. 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