Regulation of bcl-2 and fas expression in primary activation of human peripheral lymphocytes is not sensitive to dexamethasone or cyclosporin-A.
The regulation of bcl-2 and fas (Apo-1/CD95) gene product expression plays a significant role in lymphocytes proliferation, survival, and apoptosis. Dexamethasone (Dex) and the immunosuppressive agent cyclosporin-A (CsA) inhibit primary activation of lymphocytes by distinct, though overlapping mechanisms that trigger undefined signals and can induce or prevent apoptosis in lymphoid cells in vitro. Here we demonstrate that Dex and CsA, at concentrations that markedly inhibit phytohemagglutinin (PHA)-induced proliferation of normal human peripheral blood lymphocytes, suppress the activation-dependent expression of interleukin 2 (IL-2) and the alpha-chain IL-2 receptor in a dose-dependent fashion without affecting the inducible accumulation and kinetics of either bcl-2 or fas mRNAs. Similar results were obtained when PHA-stimulated lymphocytes were cultured in the presence of the CsA analogue FK-506 or rapamycin. Moreover, the inducible maximal expression of either bcl-2 or fas protein levels on 48-h PHA-activated lymphocytes was not changed in the presence of either Dex or CsA. These findings show that the cell activation-induced biosynthesis of bcl-2 and fas proteins is not affected by immunosuppressive agents, suggesting that the expression of IL-2 and both bcl-2 and fas genes is regulated through independent mechanisms.
Sfikakis
P P
PP
Research Immunology Laboratory, Athens University Medical School, Greece.
Souliotis
V L
VL
Akbar
A N
AN
Katsilambros
N
N
Hoffbrand
V A
VA
Panayiotidis
P
P
D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D010835:Phytohemagglutinins / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D019014:fas Receptor / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*
D010835:Phytohemagglutinins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D003907:Dexamethasone; D016572:Cyclosporine