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

In systemic lupus erythematosus (SLE), T helper cells exhibit increased and prolonged expression of cell-surface CD40 ligand (CD154), spontaneously ov erproduce interleukin-10 (IL-10), but underproduce interferon-gamma (IFN-ga mma). We tested the hypothesis that the imbalance of these gene products re flects skewed expression of CD154, IL-10, and IFN-gamma genes. Here, we dem onstrate that the histone deacetylase inhibitor, trichostatin A, significan tly down-regulated CD154 and IL-10 and up-regulated IFN-gamma gene expressi on 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 s kewed expression of multiple genes implicated in the immunopathogenesis of SLE suggests that this pharmacologic agent may be a candidate for the treat ment of this autoimmune disease.