期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2001
卷号：98
期号：5
页码：2628-2633
DOI：10.1073/pnas.051507098
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
