کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3297471 | 1209885 | 2008 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The Hydroxylase Inhibitor Dimethyloxalylglycine Is Protective in a Murine Model of Colitis
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کلمات کلیدی
NF-κBDSSHIFDAIDMOGdimethyloxalylglycinecIAP-2TNFcellular inhibitor of apoptosis protein 2MPO - DFOinterleukin - اینترلوکینdisease activity index - شاخص فعالیت بیماریHypoxia Inducible Factor - فاکتور قابل تشخیص هیپوکسیtumor necrosis factor - فاکتور نکروز تومورnuclear factor κB - فاکتور هسته ای κBmyeloperoxidase - میلوپراکسیداز
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Background & Aims: Prolyl and asparaginyl hydroxylases are key oxygen-sensing enzymes that confer hypoxic sensitivity to transcriptional regulatory pathways including the hypoxia inducible factor 1 (HIF-1) and nuclear factor-κB (NF-κB). Knockout of either HIF-1 or (IKKβ-dependent) NF-κB pathways in intestinal epithelial cells promotes inflammatory disease in murine models of colitis. Both HIF-1 and NF-κB pathways are repressed by the action of hydroxylases through the hydroxylation of key regulatory molecules. Methods: In this study we have investigated the effects of the hydroxylase inhibitor dimethyloxalylglycine (DMOG) on Caco-2 intestinal epithelial cells in vitro and in a dextran sodium sulfate-induced model of murine colitis. Results: DMOG induces both HIF-1 and NF-κB activity in cultured intestinal epithelial cells, and is profoundly protective in dextran-sodium sulfate colitis in a manner that is at least in part reflected by the development of an anti-apoptotic phenotype in intestinal epithelial cells, which we propose reduces epithelial barrier dysfunction. Conclusions: These data show that hydroxylase inhibitors such as DMOG represent a new strategy for the treatment of inflammatory bowel disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 134, Issue 1, January 2008, Pages 156-165.e1
Journal: Gastroenterology - Volume 134, Issue 1, January 2008, Pages 156-165.e1
نویسندگان
Eoin P. Cummins, Fergal Seeballuck, Stephen J. Keely, Niamh E. Mangan, John J. Callanan, Padraic G. Fallon, Cormac T. Taylor,