Trichostatin A reverses skewed expression of CD154, interleukin-10, and interferon-γ gene and protein expression in lupus T cells


Autoria(s): Mishra, Nilamadhab; Brown, Doris R.; Olorenshaw, Irene M.; Kammer, Gary M.
Data(s)

27/02/2001

20/02/2001

Resumo

In systemic lupus erythematosus (SLE), T helper cells exhibit increased and prolonged expression of cell-surface CD40 ligand (CD154), spontaneously overproduce interleukin-10 (IL-10), but underproduce interferon-gamma (IFN-γ). We tested the hypothesis that the imbalance of these gene products reflects skewed expression of CD154, IL-10, and IFN-γ genes. Here, we demonstrate that the histone deacetylase inhibitor, trichostatin A, significantly down-regulated CD154 and IL-10 and up-regulated IFN-γ gene expression in SLE T cells. This reversal corrected the aberrant expression of these gene products, thereby enhancing IFN-γ production and inhibiting IL-10 and CD154 expression. That trichostatin A can simultaneously reverse the skewed expression of multiple genes implicated in the immunopathogenesis of SLE suggests that this pharmacologic agent may be a candidate for the treatment of this autoimmune disease.

Identificador

/pmc/articles/PMC30189/

/pubmed/11226290

http://dx.doi.org/10.1073/pnas.051507098

Idioma(s)

en

Publicador

The National Academy of Sciences

Direitos

Copyright © 2001, The National Academy of Sciences

Palavras-Chave #Biological Sciences
Tipo

Text