The induction of IFN-gamma production and m-RNAs of interleukin 2 and IFN-gamma by phorbol esters and a calcium ionophore.
Human peripheral blood mononuclear leukocytes were found to produce large amounts of interferon-gamma in response to the calcium ionophore A23187 combined with the phorbol ester mezerein. This effect was synergistic since A23187 and mezerein separately did not induce significant interferon-gamma levels. A23187 plus mezerein induced high levels of interleukin-2 and interferon-gamma mRNAs. The presence of cyclohexamide, which inhibits protein synthesis by greater than 99%, had no effect on the induction by A23187 plus mezerein of mRNA from either gene, indicating that synthesis of proteins such as interleukin-2 is not required for activation of either gene. In addition, using different protocols of stimulation of lymphocytes it was shown that both interleukin-2 and interferon-gamma mRNA steady state levels varied in concert. We conclude that interferon-gamma and interleukin-2 genes are coordinately expressed and activation of transcription of these genes is a primary event of T cell activation independent of production of other proteins.
D000001:Calcimycin / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004224:Diterpenes; D004768:Enterotoxins / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics*; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D013211:Staphylococcus aureus; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D002273:Carcinogens; D004224:Diterpenes; D004768:Enterotoxins; D007376:Interleukin-2; D012333:RNA, Messenger; D013729:Terpenes; C011309:mezerein; C026066:enterotoxin A, Staphylococcal; D000001:Calcimycin; D007371:Interferon-gamma; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate