Effect of Trichostatin A on CD4 surface density in peripheral blood T cells.
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.
Kozłowska
Anna
A
Department of Biochemistry and Molecular Biology, University of Medical Sciences, Poznań, Poland. kozlowa@am.poznan.pl
Jagodziński
Paweł P
PP
D000107:Acetylation / Q000187:drug effects; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000378:metabolism; D015704:CD4 Antigens / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*
D015704:CD4 Antigens; D002843:Chromatin; D006657:Histones; D006877:Hydroxamic Acids; D007166:Immunosuppressive Agents; C012589:trichostatin A; D006655:Histone Deacetylases