trichostatin-a and Autoimmune-Diseases

Acetylation level of chromatin histones is maintained by histone acetylases (HATs) and deacetylases (HDACs) and correlates with transcriptional activity of genes. Trichostatin A (TSA) is HDAC inhibitor that causes various effects in cells, including immunomodulation. The CD4 antigen is a key coreceptor involved in activation of T helper cells. Using quantitative real-time PCR (RQ-PCR) and flow cytometry techniques, we estimated CD4 transcript level and density of CD4 antigen on the surface of TSA-treated stimulated and unstimulated peripheral T cells. We observed a dose dependent decrease in CD4 mRNA level and antigen density on surface of TSA-treated stimulated T cells. However, we did not observe any significant TSA effect on CD4 mRNA and protein expression in unstimulated T cells. Our data suggest that TSA may induce biosynthesis of factors responsible for negative regulation of CD4 antigen expression in stimulated T cells. Our investigation may support previous observation that this drug has immunosuppresive effect on primary T cells and may be useful in treatment of certain autoimmune disorders.

Topics: Acetylation; Autoimmune Diseases; CD4 Antigens; CD4-Positive T-Lymphocytes; Cells, Cultured; Chromatin; Down-Regulation; Histone Deacetylases; Histones; Humans; Hydroxamic Acids; Immunosuppressive Agents; Lymphocyte Activation