{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T22:02:10Z","timestamp":1768687330598,"version":"3.49.0"},"reference-count":70,"publisher":"American Physiological Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2012,6,1]]},"abstract":"<jats:p>Il-10-deficient mice develop colitis associated with exaggerated Th1\/Th17 responses and are a valuable model of inflammatory bowel disease. Mkp-1 is a major negative regulator of MAPKs, and its expression is enhanced by IL-10. To understand the role of Mkp-1 in the regulation of intestinal mucosal immune responses, we studied the effect of Mkp-1 deletion on the pathogenesis of colitis in Il-10<jats:sup>\u2212\/\u2212<\/jats:sup>mice. We found that knockout of Mkp-1 on an Il-10<jats:sup>\u2212\/\u2212<\/jats:sup>background accelerated the development of colitis. Compared with Il-10<jats:sup>\u2212\/\u2212<\/jats:sup>mice, colitis not only appeared earlier but also was more severe in Il-10<jats:sup>\u2212\/\u2212<\/jats:sup>\/ Mkp-1<jats:sup>\u2212\/\u2212<\/jats:sup>mice. Il-10<jats:sup>\u2212\/\u2212<\/jats:sup>mice exhibited a mild intestinal inflammation in the specific pathogen-free environment, and rectal prolapse rarely appeared before 6 mo of age. In contrast, the majority of Il-10<jats:sup>\u2212\/\u2212<\/jats:sup>\/ Mkp-1<jats:sup>\u2212\/\u2212<\/jats:sup>mice developed severe colitis rapidly and presented with rectal prolapse after only 2\u20133 mo. The colon of Il-10<jats:sup>\u2212\/\u2212<\/jats:sup>\/ Mkp-1<jats:sup>\u2212\/\u2212<\/jats:sup>mice showed diffuse transmural chronic inflammation and mucosal hyperplasia, with significantly more proliferating crypt epithelial cells than those of Il-10<jats:sup>\u2212\/\u2212<\/jats:sup>mice. In addition to the severe colitis, Il-10<jats:sup>\u2212\/\u2212<\/jats:sup>\/ Mkp-1<jats:sup>\u2212\/\u2212<\/jats:sup>mice also developed conjunctivitis and blepharitis. The colon of Il-10<jats:sup>\u2212\/\u2212<\/jats:sup>\/ Mkp-1<jats:sup>\u2212\/\u2212<\/jats:sup>mice contained significantly higher levels of proinflammatory cytokines and exhibited greater MAPK activities than did the colon of Il-10<jats:sup>\u2212\/\u2212<\/jats:sup>mice. Splenocytes and lymphocytes from Il-10<jats:sup>\u2212\/\u2212<\/jats:sup>\/ Mkp-1<jats:sup>\u2212\/\u2212<\/jats:sup>mice produced higher levels of Th1 cytokines ex vivo upon activation than did cells from Il-10<jats:sup>\u2212\/\u2212<\/jats:sup>mice. Our studies support a pivotal role of Mkp-1 as a negative regulator of mucosal immune responses and highlight its protective function against inflammatory bowel disease.<\/jats:p>","DOI":"10.1152\/ajpgi.00018.2012","type":"journal-article","created":{"date-parts":[[2012,3,30]],"date-time":"2012-03-30T03:03:37Z","timestamp":1333076617000},"page":"G1322-G1335","source":"Crossref","is-referenced-by-count":22,"title":["Knockout of<i>Mkp-1<\/i>exacerbates colitis in<i>Il-10<\/i>-deficient mice"],"prefix":"10.1152","volume":"302","author":[{"given":"Ranyia","family":"Matta","sequence":"first","affiliation":[{"name":"Integrated Biomedical Science Graduate Program, The Ohio State University, Columbus, Ohio;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.","family":"Barnard","sequence":"additional","affiliation":[{"name":"Integrated Biomedical Science Graduate Program, The Ohio State University, Columbus, Ohio;"},{"name":"Center for Molecular and Human Genetics, The Ohio State University College of Medicine, Columbus, Ohio;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyn M.","family":"Wancket","sequence":"additional","affiliation":[{"name":"The Veterinary Bioscience Graduate Program, The Ohio State University, Columbus, Ohio;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Yan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, P.R. 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