| IFN-{gamma} Attenuates Hypoxia-Inducible Factor (HIF) Activity in Intestinal Epithelial Cells through Transcriptional Repression of HIF-1{beta}. | |
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MedLine Citation:
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PMID: 21199896 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Numerous studies have revealed that hypoxia and inflammation occur coincidentally in mucosal disorders, such as inflammatory bowel disease. During inflammation, epithelial-expressed hypoxia-inducible factor (HIF) serves an endogenously protective function. In this study, we sought to explore how mucosal immune responses influence HIF-dependent end points. Guided by a screen of relevant inflammatory mediators, we identified IFN-γ as a potent repressor of HIF-dependent transcription in human intestinal epithelial cells. Analysis of HIF levels revealed that HIF-1β, but not HIF-1α, is selectively repressed by IFN-γ in a JAK-dependent manner. Cloning and functional analysis of the HIF-1β promoter identified a prominent region for IFN-γ-dependent repression. Further studies revealed that colonic IFN-γ and HIF-1β levels were inversely correlated in a murine colitis model. Taken together, these studies demonstrated that intestinal epithelial HIF is attenuated by IFN-γ through transcriptional repression of HIF-1β. These observations are relevant to the pathophysiology of colitis (i.e., that loss of HIF signaling during active inflammation may exacerbate disease pathogenesis). |
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Authors:
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Louise E Glover; Karina Irizarry; Melanie Scully; Eric L Campbell; Brittelle E Bowers; Carol M Aherne; Douglas J Kominsky; Christopher F Macmanus; Sean P Colgan |
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Publication Detail:
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Type: Journal Article Date: 2011-01-03 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 186 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 1790-8 Citation Subset: AIM; IM |
Affiliation:
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Mucosal Inflammation Program, Department of Medicine, University of Colorado Denver, Aurora, CO 80045; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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