| Activation of Hif-1alpha delays inflammation resolution by reducing neutrophil apoptosis and reverse migration in a zebrafish inflammation model. | |
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MedLine Citation:
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PMID: 21555741 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The oxygen sensing transcription factor HIF-1α plays a critical role in the regulation of myeloid cell function. The mechanisms of regulation are not well understood, nor the phenotypic consequences of HIF modulation in the context of neutrophilic inflammation. Species conservation across higher metazoans enables the use of the genetically tractable and transparent zebrafish embryo to study in vivo resolution of the inflammatory response. Using both a pharmacological approach known to lead to stabilization of HIF-1α, and selective genetic manipulation of zebrafish HIF-1α homologues we sought to determine the roles of HIF-1α in inflammation resolution. Both approaches reveal that activated Hif-1α delays resolution of inflammation following tail transection in zebrafish larvae. This delay can be replicated by neutrophil specific Hif activation, and is a consequence of both reduced neutrophil apoptosis, and increased retention of neutrophils at the site of tissue injury. Hif-activated neutrophils continue to patrol the injury site during the resolution phase, when neutrophils would normally migrate away. Site-directed mutagenesis of Hif in vivo reveals that hydroxylation of Hif-1α by Phd hydroxylases critically regulates the Hif pathway in zebrafish neutrophils. Our data demonstrate that Hif-1α regulates neutrophil function in complex ways during inflammation resolution in vivo. |
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Authors:
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Philip M Elks; Fredericus J van Eeden; Giles Dixon; Xingang Wang; Constantino Carlos Reyes-Aldasoro; Philip W Ingham; Moira K B Whyte; Sarah R Walmsley; Stephen A Renshaw |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-5-9 |
Journal Detail:
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Title: Blood Volume: - ISSN: 1528-0020 ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-5-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield, United Kingdom; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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