Effect of trichostatin A on human T cells resembles signaling abnormalities in T cells of patients with systemic lupus erythematosus: a new mechanism for TCR zeta chain deficiency and abnormal signaling

J Cell Biochem. 2002;85(3):459-69. doi: 10.1002/jcb.10160.

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

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • CD3 Complex / drug effects
  • CD3 Complex / metabolism
  • Calcium Signaling
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology*
  • Ephrin-A2 / drug effects
  • Ephrin-A2 / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Hydroxamic Acids / pharmacology*
  • Immunosuppressive Agents / pharmacology
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Lupus Erythematosus, Systemic / metabolism*
  • Lupus Erythematosus, Systemic / pathology
  • Membrane Proteins / deficiency*
  • Membrane Proteins / drug effects
  • Membrane Proteins / metabolism
  • Receptors, Antigen, T-Cell / deficiency*
  • Receptors, Antigen, T-Cell / drug effects
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, IgE / drug effects
  • Receptors, IgE / genetics
  • Signal Transduction* / drug effects
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology
  • Time Factors
  • Tyrosine / metabolism

Substances

  • CD3 Complex
  • Enzyme Inhibitors
  • Ephrin-A2
  • Hydroxamic Acids
  • Immunosuppressive Agents
  • Interleukin-2
  • Membrane Proteins
  • Receptors, Antigen, T-Cell
  • Receptors, IgE
  • antigen T cell receptor, zeta chain
  • trichostatin A
  • Tyrosine