{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:02:58Z","timestamp":1792800178571,"version":"4.5.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to evaluate the therapeutic effects of Ruxolitinib, a JAK1\/2 inhibitor, on DSS-induced acute colitis in mice, with a focus on its impact on disease activity, inflammatory responses, modulation of myeloid-derived suppressor cells (MDSCs), and regulation of the JAK\/STAT1 signaling pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Acute UC was induced in C57BL\/6 mice by administering a 2.5% DSS solution. Mice were randomly assigned to three groups: the blank group (no DSS), the model group (DSS only), and the Ruxolitinib-treated group (DSS +30\u00a0mg\/kg Ruxolitinib by gavage for 14 consecutive days). Body weight, disease activity index (DAI) scores, spleen weight, and colon length were measured. Spleen index and the spleen weight-to-colon length ratio were calculated. Flow cytometry was used to assess the proportion of MDSCs in the blood. <jats:italic>In vitro<\/jats:italic>, CCD841 and Jurkat cells were pretreated with 50\u00a0IU\/mL IFN-\u03b3 for 2\u00a0h, followed by 24-h treatment with Ruxolitinib. PCR array analysis was performed to identify transcriptional changes in JAK-STAT pathway-related genes. Electrophoretic mobility shift assay (EMSA) and Western blot were used to investigate the inhibition of STAT1 activation and phosphorylation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>In vivo<\/jats:italic>, DSS-induced acute colitis in the model group, and Ruxolitinib treatment significantly alleviated colitis as evidenced by reduced body weight loss (p &amp;lt; 0.05), decreased DAI scores in the later stages (p &amp;lt; 0.05), a lower spleen index (p &amp;lt; 0.05), increased colon length (p &amp;lt; 0.01), and a reduced spleen weight-to-colon length ratio (p &amp;lt; 0.05). Flow cytometry revealed a significant reduction in the proportion of CD11b<jats:sup>+<\/jats:sup> Gr-1<jats:sup>+<\/jats:sup> MDSCs in the blood of the Ruxolitinib group compared to the model group (p &amp;lt; 0.01). <jats:italic>In vitro<\/jats:italic>, PCR array analysis showed that Ruxolitinib notably downregulated the transcription of several JAK-STAT pathway-related genes, including B2M, IRF1, RQ1, SOCS1, STAT1, and STAT3, with STAT1 showing the most pronounced changes. EMSA and Western blot analysis confirmed that Ruxolitinib effectively inhibited IFN-\u03b3-induced STAT1 activation and phosphorylation in a dose-dependent manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Ruxolitinib effectively ameliorated DSS-induced acute colitis by reducing inflammation, modulating MDSC levels, and inhibiting STAT1 activation. These findings suggest that Ruxolitinib could be a promising therapeutic agent for UC, targeting both the immune response and the JAK\/STAT1 signaling pathway.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1572534","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T14:31:05Z","timestamp":1756477865000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Ruxolitinib alleviates DSS-induced acute ulcerative colitis by inhibiting STAT1 phosphorylation and reducing MDSC infiltration"],"prefix":"10.3389","volume":"16","author":[{"given":"Lu","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyue","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent Kam Wai","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.exphem.2023.07.004","article-title":"Effects of ruxolitinib on murine regulatory T cells are immune-context dependent","author":"Aggarwal","year":"2023","journal-title":"Exp. 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