Regulation of gene expression in lectin-stimulated or lymphokine-stimulated T lymphocytes. Effects of cyclosporine.
The effects of cyclosporine were examined on gene expression induced in T lymphocytes by mitogenic lectins and interleukin 2 (IL-2). Used at concentrations that inhibited proliferation of human peripheral blood lymphocytes by approximately 90%, CsA suppressed, to different extents, the phytohemagglutinin-stimulated expression of various genes, with levels of mRNAs for IL-2 being inhibited by approximately 100%, c-myc and N-ras by approximately 80%, and c-fos and IL-2 receptors by approximately 50%. Comparisons of the actions of CsA on gene expression in a cloned murine T cell (L2), stimulated with concanavalin A or IL-2, demonstrated that CsA specifically blocked the accumulation of mRNAs for the c-myc and p53 protooncogenes when induced by Con A, but not when induced by IL-2. Taken together, these findings indicate that several pathways can control the expression of a particular gene, and suggest that CsA interferes with only some of these regulatory pathways of gene expression in T lymphocytes.
D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D037102:Lectins / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000502:physiology*
D003524:Cyclosporins; D007376:Interleukin-2; D037102:Lectins; D010835:Phytohemagglutinins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D003208:Concanavalin A