Trichostatin A down-regulates ZAP-70, LAT and SLP-76 content in Jurkat T cells

We exploited Jurkat leukemia T cell clone E6-1 as a model of Trichostatin A (TSA) effect on cellular levels of ZAP-70, LAT and SLP-76 molecules involved in the signal transduction pathway from T cell receptor to nucleus. Using reverse transcription real-time quantitative PCR and Western blotting analysis we observed that TSA resulted in ZAP-70, LAT and SLP-76 transcript and protein down-regulation in Jurkat leukemia T cells. We also found that TSA reduced half-life of ZAP-70, LAT and SLP-76 mRNAs from 4.8, 3.5, and 4.8 to approximately 2.3, 1.9 and 1.7 h, respectively. Employing the protein biosynthesis inhibitor cycloheximide, we demonstrated the involvement of RNase and/or mRNA stabilization protein in ZAP-70, LAT and SLP-76 mRNAs stabilization. The effect of TSA on ZAP-70, LAT and SLP-76 content in T cells confirms an immumosuppressive effect by TSA, and the usefulness of this histone deacetylase inhibitor in the treatment of autoimmune diseases. (c) 2006 Elsevier B.V. All rights reserved.