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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
32
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pubmed:dateCreated |
2001-8-6
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pubmed:abstractText |
Glucocorticoids acting through their specific receptor can either enhance or repress gene transcription. Dexamethasone represses interleukin-1beta-stimulated histone acetylation and granulocyte-macrophage colony-stimulating factor expression through a combination of direct inhibition of p65-associated histone acetyltransferase (HAT) activity and by recruiting histone deacetylase 2 (HDAC2) to the p65-HAT complex. Here we show that mifepristone, a glucocorticoid receptor partial agonist, has no ability to induce gene expression but represses interleukin-1beta-stimulated histone acetylation and granulocyte-macrophage colony-stimulating factor release by 50% maximally. Mifepristone was able to inhibit p65-associated HAT activity to the same extent as dexamethasone but failed to inhibit the natural promoter to an equal extent due to an inability to recruit HDAC2 to the p65-associated HAT complex. These data suggest that the maximal repressive actions of glucocorticoids require recruitment of HDAC2 to a p65-HAT complex. These data also suggest that pharmacological manipulation of specific histone acetylation status is a potentially useful approach for the treatment of inflammatory diseases.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Glucocorticoids,
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Acetyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases,
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/Hormone Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Lysine,
http://linkedlifedata.com/resource/pubmed/chemical/Mifepristone,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucocorticoid,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor RelA
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
30208-15
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11395507-Acetylation,
pubmed-meshheading:11395507-Acetyltransferases,
pubmed-meshheading:11395507-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:11395507-Blotting, Western,
pubmed-meshheading:11395507-Cell Nucleus,
pubmed-meshheading:11395507-Chromatin,
pubmed-meshheading:11395507-Dexamethasone,
pubmed-meshheading:11395507-Dose-Response Relationship, Drug,
pubmed-meshheading:11395507-Enzyme Activation,
pubmed-meshheading:11395507-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:11395507-Glucocorticoids,
pubmed-meshheading:11395507-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:11395507-Histone Acetyltransferases,
pubmed-meshheading:11395507-Histone Deacetylase 2,
pubmed-meshheading:11395507-Histone Deacetylases,
pubmed-meshheading:11395507-Histones,
pubmed-meshheading:11395507-Hormone Antagonists,
pubmed-meshheading:11395507-Humans,
pubmed-meshheading:11395507-Immunohistochemistry,
pubmed-meshheading:11395507-Inflammation,
pubmed-meshheading:11395507-Interleukin-1,
pubmed-meshheading:11395507-Lysine,
pubmed-meshheading:11395507-Mifepristone,
pubmed-meshheading:11395507-NF-kappa B,
pubmed-meshheading:11395507-Precipitin Tests,
pubmed-meshheading:11395507-Protein Binding,
pubmed-meshheading:11395507-Receptors, Glucocorticoid,
pubmed-meshheading:11395507-Repressor Proteins,
pubmed-meshheading:11395507-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:11395507-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:11395507-Transcription, Genetic,
pubmed-meshheading:11395507-Transcription Factor RelA,
pubmed-meshheading:11395507-Tumor Cells, Cultured
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pubmed:year |
2001
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pubmed:articleTitle |
p65-activated histone acetyltransferase activity is repressed by glucocorticoids: mifepristone fails to recruit HDAC2 to the p65-HAT complex.
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pubmed:affiliation |
Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, Dovehouse St., London SW3 6LY, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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