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The histone deacetylase inhibitor trichostatin A upregulates regulatory T cells and modulates autoimmunity in NZB/W F1 mice
- Source :
-
Journal of Autoimmunity . Sep2008, Vol. 31 Issue 2, p123-130. 8p. - Publication Year :
- 2008
-
Abstract
- Abstract: We sought to determine if the histone deacetylase inhibitor (HDI), trichostatin A (TSA), would alter systemic lupus erythematosus (SLE) in NZB/W mice. Fourteen to sixteen-week-old female NZB/W F1 mice were given TSA (1.0mg/kg body weight (BW)) intraperitonealy (i.p.) daily, TSA (1.0mg/kg BW) i.p.+anti-CD25 (250mg/mouse) i.p. every third day, only anti-CD25 (250mg/mouse) i.p., DMSO or isotype IgG. Disease progression was assessed as they aged. Mice were sacrificed at 26 or 38 weeks of age, tissues collected and evaluated. At 36 weeks, TSA-treated animals had decreased anti-double stranded DNA (dsDNA) autoantibodies and decreased protein excretion compared to controls. Spleen size and the percentage of CD4+CD69+ cells were decreased, with an increase in CD4+CD25+ T cells in the TSA-treated mice. Real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis of T cells showed a decrease in IL-6 production but an increase in TGF-β1 and Foxp3 in the TSA-treated animals. Kidney analysis showed a decrease in IgG and C3 deposition, decrease in pathologic glomerular disease and renal MCP-1, MMP-9, and IL-6 mRNA expression. Anti-CD25-treated mice euthanized at 26 weeks of age showed decreased Foxp3+CD4+CD25+ T cells compared to TSA-treated mice. These data suggest TSA administration modulates lupus-like disease, in part, by increasing T regulatory cells. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 08968411
- Volume :
- 31
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Autoimmunity
- Publication Type :
- Academic Journal
- Accession number :
- 34211086
- Full Text :
- https://doi.org/10.1016/j.jaut.2008.04.020