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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2004-9-9
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pubmed:abstractText |
Epigenetic regulation of gene expression is involved in the development of many diseases. Histone acetylation is a posttranslational modification of the nucleosomal histone tails that is regulated by the balance of histone deacetylases and histone acetyltransferases. Alterations in the balance of histone acetylation have been shown to cause aberrant expression of genes that are a hallmark of many diseases, including systemic lupus erythematosus. In this study, we determined whether suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor: 1) inhibits inflammatory mediator production in vitro and 2) modulates lupus progression in vivo. Mesangial cells isolated from 10-wk-old MRL/lpr mice were stimulated with LPS/IFN-gamma and incubated with SAHA. TNF-alpha, IL-6, NO, and inducible NO synthase expression were inhibited by SAHA. We then treated MRL/lpr mice with daily injections of SAHA from age 10 to 20 wk. The animals treated with SAHA had decreased spleen size and a concomitant decrease in CD4-CD8- (double-negative) T cells compared with controls. Serum autoantibody levels and glomerular IgG and C3 deposition in SAHA-treated mice were similar to controls. In contrast, proteinuria and pathologic renal disease were significantly inhibited in the mice receiving SAHA. These data indicate that SAHA blocks mesangial cell inflammatory mediator production in vitro and disease progression in vivo in MRL/lpr mice.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD3,
http://linkedlifedata.com/resource/pubmed/chemical/Autoantibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class II,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Inflammation Mediators,
http://linkedlifedata.com/resource/pubmed/chemical/vorinostat
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2004 The American Association of Immunologists, Inc.
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
173
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4171-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15356168-Adjuvants, Immunologic,
pubmed-meshheading:15356168-Animals,
pubmed-meshheading:15356168-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:15356168-Antigens, CD3,
pubmed-meshheading:15356168-Autoantibodies,
pubmed-meshheading:15356168-CD4-Positive T-Lymphocytes,
pubmed-meshheading:15356168-CD8-Positive T-Lymphocytes,
pubmed-meshheading:15356168-Cells, Cultured,
pubmed-meshheading:15356168-Disease Progression,
pubmed-meshheading:15356168-Female,
pubmed-meshheading:15356168-Glomerular Mesangium,
pubmed-meshheading:15356168-Histocompatibility Antigens Class II,
pubmed-meshheading:15356168-Histone Deacetylase Inhibitors,
pubmed-meshheading:15356168-Hydroxamic Acids,
pubmed-meshheading:15356168-Immunosuppressive Agents,
pubmed-meshheading:15356168-Inflammation Mediators,
pubmed-meshheading:15356168-Injections, Intraperitoneal,
pubmed-meshheading:15356168-Lupus Erythematosus, Systemic,
pubmed-meshheading:15356168-Lymphopenia,
pubmed-meshheading:15356168-Mice,
pubmed-meshheading:15356168-Mice, Inbred MRL lpr,
pubmed-meshheading:15356168-Organ Size,
pubmed-meshheading:15356168-Proteinuria,
pubmed-meshheading:15356168-Spleen
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pubmed:year |
2004
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pubmed:articleTitle |
Modulation of renal disease in MRL/lpr mice by suberoylanilide hydroxamic acid.
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pubmed:affiliation |
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University and Edward Via College of Osteopathic Medicine, Blacksburg, 24060, USA. chreilly@vcom.vt.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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