| Inhibition of N-terminal ATPase on HSP90 attenuates colitis through enhanced Treg function. | |
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MedLine Citation:
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PMID: 23321985 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Inflammatory bowel disease (IBD) is a chronic inflammatory condition thought to reflect a failure of the enteral immune system to adequately regulate itself. Inflammatory stress drives upregulation of heat-shock proteins (HSPs), including the pro-inflammatory chaperone, HSP90. This protein sequesters the transcription factor, heat-shock factor 1 (HSF1) in the cytoplasm preventing transcription of a number of anti-inflammatory proteins. We hypothesized that inhibition of HSP90 would exert an anti-inflammatory effect and thereby attenuate intestinal inflammation in murine models of IBD. Inhibition of HSP90 with 17-allylaminogeldanamycin (17-AAG) reduced inflammation in acute dextran sodium sulfate and chronic CD45RB(High) colitis models coinciding with increased interleukin (IL)-10 production in the colon. Regulatory T cells (Tregs) from mice treated with 17-AAG demonstrated significantly greater suppressive capacity in vitro abolished in HSF1(-/-) or IL-10(-/-) cells. Finally, Tregs treated with 17-AAG exhibited increased nuclear localization of HSF1 with resultant upregulation of HSF1 response genes, including HSP70, HSP90 and IL-10.Mucosal Immunology advance online publication 16 January 2013. doi:10.1038/mi.2012.134. |
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Authors:
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C B Collins; C M Aherne; A Yeckes; K Pound; H K Eltzschig; P Jedlicka; E F de Zoeten |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-16 |
Journal Detail:
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Title: Mucosal immunology Volume: - ISSN: 1935-3456 ISO Abbreviation: Mucosal Immunol Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101299742 Medline TA: Mucosal Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA [2] Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado, USA [3] Children's Hospital Colorado, Digestive Health Institute, Aurora, Colorado, USA. |
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