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RP105\/MD\u20101 complex negatively regulates toll\u2010like receptor 4 (TLR4) signaling and is involved in several immune disorders. However, the precise role of MD\u20101 in inflammatory bowel diseases (IBD) remains poorly understood. To further investigate the involvement of MD\u20101 in IBD, we inhibited MD\u20101 in colon with antisense oligonucleotide (AS\u2010ODN) and assessed the effect of MD\u20101 inhibition on dextran sodium sulfate (DSS)\u2010induced colitis. We discovered that MD\u20101 protein expression was remarkably decreased in both patients with ulcerative colitis and mice with DSS\u2010induced colitis. For the first time, we showed that oral administration of MD\u20101 AS\u2010ODN to mice significantly suppressed the MD\u20101 protein levels in colon rather than systemic tissues. Subsequently, we found that MD\u20101 AS\u2010ODN treated mice were more susceptible to DSS\u2010induced colitis based on loss of body weight, colon length, histological scores, and disease activity index. MD\u20101 inhibition also significantly enhanced inflammatory cytokines production such as IL\u20106 and IL\u20101\u03b2 in colons. Finally, mice treated with MD\u20101 AS\u2010ODN exhibited increased messenger RNA levels of TLR4 and MyD88 after DSS exposure and showed enhanced nuclear factor (NF)\u2010\u03baB activation compared with the control. Taken together, specifically suppression of MD\u20101 in colon tissues with AS\u2010ODN exacerbates DSS\u2010induced experimental colitis in mice, which is possibly related to activation of TLR4\/NF\u2010\u03baB signaling.<\/jats:p>","DOI":"10.1002\/jcb.28947","type":"journal-article","created":{"date-parts":[[2019,5,19]],"date-time":"2019-05-19T03:16:33Z","timestamp":1558235793000},"page":"16888-16899","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Inhibition of myeloid differentiation 1 specifically in colon with antisense oligonucleotide exacerbates dextran sodium sulfate\u2010induced colitis"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3959-3467","authenticated-orcid":false,"given":"Xiaoxing","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Zhongnan Hospital of Wuhan University  Wuhan Hubei People's Republic of 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