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

N Mishra, DR Brown, IM Olorenshaw… - Proceedings of the …, 2001 - National Acad Sciences
N Mishra, DR Brown, IM Olorenshaw, GM Kammer
Proceedings of the National Academy of Sciences, 2001National Acad Sciences
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 …
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.
National Acad Sciences