| Interferon regulatory factor 1 mediates acetylation and release of high mobility group box 1 from hepatocytes during murine liver ischemia-reperfusion injury. | |
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MedLine Citation:
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PMID: 20856174 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Damage-associated molecular patterns (DAMPs) initiate inflammatory pathways that are common to both sterile and infectious processes. The DAMP, high-mobility group box 1 (HMGB1), and the transcription factor, interferon regulatory factor 1 (IRF-1), have been independently associated as key players in ischemia-reperfusion (I/R) injury. Our study demonstrates that IRF-1 contributes to hepatocellular release of HMGB1 and further that IRF-1 is a necessary component of HMGB1 release in response to hypoxia or after liver I/R. We also link the nuclear upregulation of IRF-1 to the presence of functional Toll-like receptor 4 (TLR4), a pattern recognition receptor also important in sterile and infectious processes. Using IRF-1 chimeric mice, we show that IRF-1 upregulation in hepatic parenchymal cells, and not in the bone marrow-derived immune cells, is responsible for HMGB1 release during ischemic liver injury. Finally, our study also demonstrates a role for IRF-1 in modulating the acetylation status and subsequent release of HMGB1 through histone acetyltransferases. We found that serum HMGB1 is acetylated after liver I/R and that this process was dependent on IRF-1. Additionally, liver I/R induced a direct association of IRF-1 and the nuclear histone acetyltransferase enzyme p300. Together, these findings suggest that I/R-induced release of acetylated HMGB1 is a process that is dependent on TLR4-mediated upregulation of IRF-1. |
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Authors:
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Rajeev Dhupar; John R Klune; John Evankovich; Jon Cardinal; Matthew Zhang; Mark Ross; Noriko Murase; David A Geller; Timothy R Billiar; Allan Tsung |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Shock (Augusta, Ga.) Volume: 35 ISSN: 1540-0514 ISO Abbreviation: Shock Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421564 Medline TA: Shock Country: United States |
Other Details:
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Languages: eng Pagination: 293-301 Citation Subset: IM |
Affiliation:
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Departments of *Surgery, and †Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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