Abstract
Trichostatin A (TSA) is a potent reversible inhibitor of histone deacetylase, and it has been reported to have variable effects on the expression of a number of genes. In this report, we show that TSA suppresses the expression of the T cell receptor zeta chain gene, whereas, it upregulates the expression if its homologous gene Fc(epsilon) receptor I gamma chain. These effects are associated with decreased intracytoplasmic-free calcium responses and altered tyrosine phosphorylation pattern of cytosolic proteins. Along with these effects, we report that TSA suppresses the expression of the interleukin-2 gene. The effects of TSA on human T cells are predominantly immunosuppressive and reminiscent of the signaling aberrations that have been described in patients with systemic lupus erythematosus.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adolescent
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Adult
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CD3 Complex / drug effects
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CD3 Complex / metabolism
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Calcium Signaling
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Cells, Cultured
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Enzyme Inhibitors / pharmacology*
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Ephrin-A2 / drug effects
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Ephrin-A2 / metabolism
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Gene Expression Regulation / drug effects
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Humans
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Hydroxamic Acids / pharmacology*
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Immunosuppressive Agents / pharmacology
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Interleukin-2 / genetics
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Interleukin-2 / metabolism
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Lupus Erythematosus, Systemic / metabolism*
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Lupus Erythematosus, Systemic / pathology
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Membrane Proteins / deficiency*
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Membrane Proteins / drug effects
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Membrane Proteins / metabolism
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Receptors, Antigen, T-Cell / deficiency*
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Receptors, Antigen, T-Cell / drug effects
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Receptors, Antigen, T-Cell / metabolism
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Receptors, IgE / drug effects
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Receptors, IgE / genetics
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Signal Transduction* / drug effects
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T-Lymphocytes / drug effects
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T-Lymphocytes / metabolism*
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T-Lymphocytes / pathology
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Time Factors
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Tyrosine / metabolism
Substances
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CD3 Complex
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Enzyme Inhibitors
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Ephrin-A2
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Hydroxamic Acids
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Immunosuppressive Agents
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Interleukin-2
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Membrane Proteins
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Receptors, Antigen, T-Cell
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Receptors, IgE
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antigen T cell receptor, zeta chain
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trichostatin A
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Tyrosine