A role for protein kinase C activity in interleukin-1 (IL-1) induction of IL-2 gene expression but not in IL-1 signal transduction.
Interleukin-1 (IL-1) is known to synergize with phorbol esters in the induction of interleukin-2 (IL-2) expression in T-lymphoid leukemia cells and proliferation of mouse thymocytes. We used a plasmid construct containing the bacterial gene for chloramphenicol acetyltransferase under the control of the human IL-2 promoter to study the nature of this synergism in the murine thymoma cell line EL4. Although IL-1 induction of the IL-2 promoter in these cells required costimulus with phorbol myristate acetate, the signal induced by IL-1 was qualitatively different. We provide evidence to support the hypothesis that the phorbol ester signal is mediated by protein kinase C, and we show that the IL-1 signal is not. That IL-1 and phorbol myristate acetate represent different stimuli was shown by their response to protein kinase C inhibitors, capacity to synergize with increased intracellular free calcium, and requirement for protein synthesis. In addition we show that pretreatment with IL-1 can prime EL4 cells to subsequent activation by concentrations of phorbol esters not normally sufficient to induce IL-2 expression. Pretreated cells remained primed for at least 40 h after removal of the IL-1. Neither phorbol myristate acetate nor a calcium ionophore was capable of preactivating EL4 cells.
Sclavo Research Centre, Siena, Italy.
G
G
Macchia
C T
CT
Baldari
A
A
Massone
J L
JL
Telford
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003513:Cycloheximide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000235:genetics*; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D009693:Nucleic Acid Hybridization; D010879:Piperazines / Q000494:pharmacology; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D011493:Protein Kinase C / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D007375:Interleukin-1; D007376:Interleukin-2; D007546:Isoquinolines; D010879:Piperazines; D012313:RNA; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D003513:Cycloheximide; D015500:Chloramphenicol O-Acetyltransferase; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate