No abstract

In our present studies we sought to determine if the histone deacetylase inhibitor (HDI), trichostatin A (TSA), would alter systemic lupus erythematosus (SLE) in NZB/W mice by regulating CD4+CD25+ T‐regulatory cells. Fourteen to sixteen‐week‐old female NZB/W mice were injected with TSA (1.0 mg/kg BW) intraperitoneally (i.p.) daily, anti‐CD25 (250 mg/mouse) i.p. weekly, both TSA (1.0 mg/kg BW) and anti‐CD25 (250 mg/mouse) i.p. bi‐weekly, or untreated. The mice were monitored for various disease parameters as they aged. Mice were sacrificed at either 26 or 36 weeks of age, tissues collected and assessed for various parameters of disease. Flow cytometric analysis of splenic tissue showed TSA treated mice exhibited increased FOXP3 expression and increased CD4+CD25+ T‐regulatory cells. At 36 weeks, TSA treated animals had decreased anti‐double stranded DNA autoantibodies and decreased protein excretion. Renal pathology showed a decrease in IgG and C3 deposition in renal tissue and a decrease in pathologic glomerular disease in the TSA treated mice. These data indicate TSA decreases lupus nephritis by upregulating FOXP3 expression and CD4+CD25+T cells in NZB/W mice. Taken together, these data show TSA administration modulates lupus in part by increasing T‐regulatory cell function, and warrants further investigation as to its potential in treating SLE.