STANDARD_NAME MOREIRA_RESPONSE_TO_TSA_DN SYSTEMATIC_NAME M3506 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/MOREIRA_RESPONSE_TO_TSA_DN NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Down-regulated in CD4+ [GeneID=920] T lymphocytes after 4 h treatment with 100 nM TSA [PubChem=5562]. DESCRIPTION_FULL BACKGROUND: Histone deacetylase inhibitors (HDACIs) induce hyperacetylation of core histones modulating chromatin structure and affecting gene expression. These compounds are also able to induce growth arrest, cell differentiation, and apoptotic cell death of tumor cells in vitro as well as in vivo. Even though several genes modulated by HDAC inhibition have been identified, those genes clearly responsible for the biological effects of these drugs have remained elusive. We investigated the pharmacological effect of the HDACI and potential anti-cancer agent Trichostatin A (TSA) on primary T cells. METHODS: To ascertain the effect of TSA on resting and activated T cells we used a model system where an enriched cell population consisting of primary T-cells was stimulated in vitro with immobilized anti-CD3/anti-CD28 antibodies whilst exposed to pharmacological concentrations of Trichostatin A. RESULTS: We found that this drug causes a rapid decline in cytokine expression, accumulation of cells in the G1 phase of the cell cycle, and induces apoptotic cell death. The mitochondrial respiratory chain (MRC) plays a critical role in the apoptotic response to TSA, as dissipation of mitochondrial membrane potential and reactive oxygen species (ROS) scavengers block TSA-induced T-cell death. Treatment of T cells with TSA results in the altered expression of a subset of genes involved in T cell responses, as assessed by microarray gene expression profiling. We also observed up- as well as down-regulation of various costimulatory/adhesion molecules, such as CD28 and CD154, important for T-cell function. CONCLUSIONS: Taken together, our findings indicate that HDAC inhibitors have an immunomodulatory potential that may contribute to the potency and specificity of these antineoplastic compounds and might be useful in the treatment of autoimmune disorders. PMID 14606959 GEOID AUTHORS Moreira JM,Scheipers P,Sørensen P CONTRIBUTOR John Newman CONTRIBUTOR_ORG University of Washington EXACT_SOURCE Fig. 7A: arrow down FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS ALPL,CD247,CD3D,CD3E,CX3CR1,ENTPD2,FGF18,ICAM1,IL2RA,LAT,METAP2,NOTCH1,NOTCH2,OGDH,RARB,SLC3A2,WNT4,WNT7A GENE_SYMBOLS ALPL,CD247,CD3D,CD3E,CX3CR1,ENTPD2,FGF18,ICAM1,IL2RA,LAT,METAP2,NOTCH1,NOTCH2,OGDH,RARB,SLC3A2,WNT4,WNT7A FOUNDER_NAMES