{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:04:28Z","timestamp":1791353068865,"version":"4.3.1"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,3,28]],"date-time":"2014-03-28T00:00:00Z","timestamp":1395964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ministry of Health and Welfare, Republic of Korea (Korean Health Technology R&D Project)","award":["A092258"],"award-info":[{"award-number":["A092258"]}]},{"name":"Institute of Clinical Medicine Research, Bucheon St. Mary's Hospital Research Fund","award":["BCMC13YA07"],"award-info":[{"award-number":["BCMC13YA07"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Rebamipide, a gastroprotective agent, has the ability to scavenge reactive oxygen radicals. Increased oxidative stress is implicated in the pathogenesis of rheumatoid arthritis (RA). We undertook this study to investigate the impact of rebamipide on the development of arthritis and the pathophysiologic mechanisms by which rebamipide attenuates arthritis severity in a murine model of RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Collagen\u2010induced arthritis (CIA) was induced in DBA\/1J mice. Anti\u2013type II collagen antibody titers and interleukin\u201017 (IL\u201017) levels were determined using enzyme\u2010linked immunosorbent assay. The expression of transcription factors was analyzed by immunostaining and Western blotting. Frequencies of IL\u201017\u2013producing CD4+ T cells (Th17 cells) and CD4+CD25+FoxP3+ Treg cells were analyzed by flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Rebamipide reduced the clinical arthritis score and severity of histologic inflammation and cartilage destruction in a dose\u2010dependent manner. The joints isolated from rebamipide\u2010treated mice with CIA showed decreased expression of nitrotyrosine, an oxidative stress marker. Rebamipide\u2010treated mice showed lower circulating levels of type II collagen\u2013specific IgG, IgG1, and IgG2a. Whereas the number of Th17 cells in spleens was decreased in rebamipide\u2010treated mice with CIA, a significant increase in the number of Treg cells in spleens was observed. In vitro, rebamipide inhibited Th17 cell differentiation through STAT\u20103\/retinoic acid receptor\u2013related orphan nuclear receptor \u03b3t and reciprocally induced Treg cell differentiation through FoxP3. Rebamipide increased Nrf2 nuclear activities in murine CD4+ T cells and LBRM\u201033 murine T lymphoma cells. Heme oxygenase 1 (HO\u20101) expression in the spleens was markedly increased in rebamipide\u2010treated mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The inhibitory effects of rebamipide on joint inflammation are associated with recovery from an imbalance between Th17 cells and Treg cells and with activation of an Nrf2\/HO\u20101 antioxidant pathway.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38310","type":"journal-article","created":{"date-parts":[[2013,12,10]],"date-time":"2013-12-10T14:47:38Z","timestamp":1386686858000},"page":"874-885","source":"Crossref","is-referenced-by-count":49,"title":["Rebamipide Suppresses Collagen\u2010Induced Arthritis Through Reciprocal Regulation of Th17\/Treg Cell Differentiation and Heme Oxygenase 1 Induction"],"prefix":"10.1002","volume":"66","author":[{"given":"Su\u2010Jin","family":"Moon","sequence":"first","affiliation":[{"name":"Catholic University of Korea Seoul South 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