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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 ζ chain deficiency and abnormal signaling * †
Author(s) -
Nambiar Madhusoodana P.,
Warke Vishal G.,
Fisher Carolyn U.,
Tsokos George C.
Publication year - 2002
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10160
Subject(s) - trichostatin a , t cell receptor , histone deacetylase inhibitor , signal transduction , tyrosine phosphorylation , microbiology and biotechnology , phosphorylation , biology , cancer research , histone deacetylase , t cell , chemistry , immunology , gene , histone , immune system , genetics
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 ζ chain gene, whereas, it upregulates the expression if its homologous gene Fcε receptor I γ 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. J. Cell. Biochem. 85: 459–469, 2002. Published 2002 Wiley‐Liss, Inc.