alexa Trichostatin A reverses skewed expression of CD154, interleukin-10, and interferon-gamma gene and protein expression in lupus T cells.
Immunology

Immunology

Rheumatology: Current Research

Author(s): Mishra N, Brown DR, Olorenshaw IM, Kammer GM

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Abstract 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-gamma). We tested the hypothesis that the imbalance of these gene products reflects skewed expression of CD154, IL-10, and IFN-gamma genes. Here, we demonstrate that the histone deacetylase inhibitor, trichostatin A, significantly down-regulated CD154 and IL-10 and up-regulated IFN-gamma gene expression in SLE T cells. This reversal corrected the aberrant expression of these gene products, thereby enhancing IFN-gamma 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.
This article was published in Proc Natl Acad Sci U S A and referenced in Rheumatology: Current Research

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