| Histone deacetylase 3 is an epigenomic brake in macrophage alternative activation. | |
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MedLine Citation:
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PMID: 22156208 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Macrophages, a key cellular component of inflammation, become functionally polarized in a signal- and context-specific manner. Th2 cytokines such as interleukin 4 (IL-4) polarize macrophages to a state of alternative activation that limits inflammation and promotes wound healing. Alternative activation is mediated by a transcriptional program that is influenced by epigenomic modifications, including histone acetylation. Here we report that macrophages lacking histone deacetylase 3 (HDAC3) display a polarization phenotype similar to IL-4-induced alternative activation and, furthermore, are hyperresponsive to IL-4 stimulation. Throughout the macrophage genome, HDAC3 deacetylates histone tails at regulatory regions, leading to repression of many IL-4-regulated genes characteristic of alternative activation. Following exposure to Schistosoma mansoni eggs, a model of Th2 cytokine-mediated disease that is limited by alternative activation, pulmonary inflammation was ameliorated in mice lacking HDAC3 in macrophages. Thus, HDAC3 functions in alternative activation as a brake whose release could be of benefit in the treatment of multiple inflammatory diseases. |
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Authors:
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Shannon E Mullican; Christine A Gaddis; Theresa Alenghat; Meera G Nair; Paul R Giacomin; Logan J Everett; Dan Feng; David J Steger; Jonathan Schug; David Artis; Mitchell A Lazar |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Genes & development Volume: 25 ISSN: 1549-5477 ISO Abbreviation: Genes Dev. Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-13 Completed Date: 2012-02-10 Revised Date: 2012-04-03 |
Medline Journal Info:
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Nlm Unique ID: 8711660 Medline TA: Genes Dev Country: United States |
Other Details:
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Languages: eng Pagination: 2480-8 Citation Subset: IM |
Affiliation:
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Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Epigenesis, Genetic* Histone Deacetylases / genetics*, metabolism Interleukin-4 / genetics, metabolism Macrophage Activation / genetics* Macrophages / immunology, metabolism* Mice Mice, Inbred Strains Pneumonia / enzymology, immunology, parasitology Schistosoma mansoni Th2 Cells / immunology, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AI61570/AI/NIAID NIH HHS; DK07314/DK/NIDDK NIH HHS; DK19525/DK/NIDDK NIH HHS; DK43806/DK/NIDDK NIH HHS; DK43806S1/DK/NIDDK NIH HHS; DK49210/DK/NIDDK NIH HHS; R37 DK043806-21/DK/NIDDK NIH HHS; R37 DK043806-22/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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207137-56-2/Interleukin-4; EC 3.5.1.98/Histone Deacetylases; EC 3.5.1.98/histone deacetylase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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