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 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.
Section on Rheumatology and Clinical Immunology, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
N
N
Mishra
D R
DR
Brown
I M
IM
Olorenshaw
G M
GM
Kammer
D000328:Adult; D001483:Base Sequence; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D017931:DNA Primers; D005260:Female; D005803:Genes, Immunoglobulin; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D017931:DNA Primers; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D016753:Interleukin-10; D023201:CD40 Ligand; C012589:trichostatin A; D007371:Interferon-gamma