Enhanced Mucosal Defense and Reduced Tumor Burden in Mice with the Compromised Negative Regulator IRAK-M

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• 作者：Daniel E. Rothschild^a ; Yao Zhang^b ; Na Diao^b ; Christina K. Lee^b ; Keqiang Chen^b ; Clayton C. Caswell^a ; Daniel J. Slade^c ; Richard F. Helm^c ; Tanya LeRoith^a ; Liwu Li^b ; ^lwli@vt.edu ; Irving C. Allen^a ; ^{icallen@vt.edu}
• 关键词：Colitis ; Colitis associated cancer ; GALT ; Inflammatory bowel disease ; IRAK-M
• 刊名：EBioMedicine
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：15
• 期：Complete
• 页码：36-47
• 全文大小：1895 K
• 卷排序：15

文摘

Human patients display increased IRAK-M expression during IBD and colorectal cancer. Irak-m−/− mice are protected from colitis and colitis associated tumorigenesis. Irak-m splice variant robustly activates NF-κB signaling.Abnormal inflammatory responses in the gut can lead to the progression of severe diseases such as inflammatory bowel disease and colitis associated cancer. In order to improve the treatment options for patients afflicted with these diseases, we investigated a protein termed interleukin receptor associated kinase M (IRAK-M) that is implicated in the regulation of inflammation. In this study, we used mice as a model system to gain insight into the contribution of IRAK-M to colitis and colitis-associated cancer pathogenesis. Our findings suggest mice containing a mutant IRAK-M are protected against both ulcerative colitis and colitis associated cancer.