Gene Set: MOREIRA_RESPONSE_TO_TSA_DN

Standard name MOREIRA_RESPONSE_TO_TSA_DN
Systematic name M3506
Brief description Down-regulated in CD4+ [GeneID=920] T lymphocytes after 4 h treatment with 100 nM TSA [PubChem=5562].
Full description or abstract 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.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 14606959   Authors: Moreira JM,Scheipers P,Sørensen P
Exact source Fig. 7A: arrow down
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Organism Homo sapiens
Contributed by John Newman (University of Washington)
Source platform HUMAN_GENE_SYMBOL
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Version history 3.0: Renamed from TSA_CD4_DN

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