{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T23:26:19Z","timestamp":1792106779633,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sepsis is perceived as lethal tissue damage and significantly increases mortality in combination with acute kidney injury (AKI). M2 macrophages play important roles in the secretion of anti\u2010inflammatory and tissue repair mediators. We aimed to study the role of Dehydroandrographolide (Deh) in sepsis\u2010associated AKI in vitro and in vivo through lipopolysaccharide (LPS)\u2010induced macrophages model and cecal ligation and puncture\u2010induced AKI mice model, and to reveal the mechanism related to M2 macrophage polarization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Enzyme\u2010linked immunosorbent assay kits were used to assess the levels of inflammatory factors. Expression of markers related to M1 macrophages and M2 macrophages were analyzed. Additionally, dual specificity phosphatase 3 (DUSP3) expression was tested. Cell apoptosis was evaluated by flow cytometry analysis and terminal\u2010deoxynucleotidyl transferase\u2010mediated nick end labeling staining. Moreover, renal histological assessment was performed by using hematoxylin and eosin staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Deh reduced inflammation of THP\u20101\u2010derived macrophages exposed to LPS. Besides, Deh induced the polarization of M1 macrophages to M2 and downregulated DUSP3 expression in THP\u20101\u2010derived macrophages under LPS conditions. Further, DUSP3 overexpression reversed the impacts of Deh on the inflammation and M2 macrophages polarization of THP\u20101\u2010derived macrophages stimulated by LPS. Additionally, human proximal tubular epithelial cells (HK\u20102) in the condition medium from DUSP3\u2010overexpressed THP\u20101\u2010derived macrophages treated with LPS and Deh displayed decreased viability and increased apoptosis and inflammation. The in vivo results suggested that Deh improved the renal function, ameliorated pathological injury, induced the polarization of M1 macrophages to M2, suppressed inflammation and apoptosis, and downregulated DUSP3 expression in sepsis\u2010induced mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Deh facilitated M2 macrophage polarization by downregulating DUSP3 to inhibit septic AKI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.1249","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T08:14:33Z","timestamp":1713341673000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Dehydroandrographolide facilitates M2 macrophage polarization by downregulating DUSP3 to inhibit sepsis\u2010associated acute kidney 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