{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:44:37Z","timestamp":1792115077854,"version":"4.4.0"},"reference-count":22,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T00:00:00Z","timestamp":1715644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["226\u20102023\u201000072"],"award-info":[{"award-number":["226\u20102023\u201000072"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300582"],"award-info":[{"award-number":["82300582"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>Cenicriviroc (CVC) is a CCR2\/CCR5 antagonist that has been shown to be effective in the treatment of inflammatory and fibrotic diseases. Our study evaluated its efficacy in colitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mouse models of DSS\u2010induced acute and chronic colitis were established. The efficacy of CVC in colitis was assessed by disease activity index (DAI) scores, histological assessment of inflammation and fibrosis, and expression assays of key molecules. In in vitro experiments, HT29 cell line was exposed to TNF\u03b1 to study inflammatory signaling in intestinal epithelial cells. CCD\u201018Co colonic myofibroblasts and human primary colonic fibroblasts were activated by TGF\u03b21 to mimic fibroblast activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In HT29 cells, CVC significantly reduced mRNA expression of CCL5 (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) but had no effect on CCL2. Furthermore, CVC reduced downstream CX3CL1 (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and TNF\u03b1 (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) expression, thereby inhibiting inflammatory progression. In acute colitis mice, CVC significantly reduced DAI scores and serum TNF\u03b1 levels (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and attenuated colonic inflammation as shown by HE staining. Meanwhile, CVC had no adverse effects on the liver, heart, and kidney of mice. On the other hand, in cellular models of chronic colitis, CVC decreased the expression of fibrosis markers, including FN, CTGF, \u03b1\u2010SMA, and MMP9, and inhibited TGF\u03b21\u2010induced fibrotic activation (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). In addition, CVC attenuated colonic fibrosis in chronic colitis mice. Moreover, CVC significantly promoted autophagy, which contributed to its regulation of inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>CVC significantly inhibited inflammation through CCL5\/CCR5 signaling without damaging vital organs and suppressed fibrotic activation in chronic colitis, suggesting its great potential to relieve colonic inflammation and fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.16622","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:46:52Z","timestamp":1715734012000},"page":"1597-1605","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["CCR2\/CCR5 antagonist cenicriviroc reduces colonic inflammation and fibrosis in experimental colitis"],"prefix":"10.1111","volume":"39","author":[{"given":"Xin","family":"Song","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chensheng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Fourth Affiliated Hospital Zhejiang University School of Medicine  Yiwu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengli","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Fourth Affiliated Hospital Zhejiang University School of Medicine  Yiwu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4025-8095","authenticated-orcid":false,"given":"Xinjue","family":"He","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,14]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30333-4"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-022-00658-y"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.07.026"},{"key":"e_1_2_5_5_1","first-page":"8561","article-title":"The role of chemokines and adipokines as biomarkers of Crohn's disease activity: a systematic review of the literature","volume":"13","author":"Mello JDC","year":"2021","journal-title":"Am. 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