Interleukin 2 induction of interferon-gamma mRNA synthesis.
Interleukin 2 (IL 2) induces specific mRNA synthesis and secretion of an important immunoregulatory molecule, interferon-gamma (IFN-gamma). We have observed that treatment of an IL 2 independent murine T cell line, BUD-27, with IL 2, calcium ionophore A23187, or agents that activate phospholipid/Ca2+-dependent protein kinase C results in increased IFN-gamma mRNA transcription and release of anti-viral activity. These same agents each induced the subcellular redistribution of protein kinase C from cytosol to plasma membrane in both the BUD-27 cell line and its IL 2-dependent parent, CT6. Ionophore concentrations greater than 1 micron exhibited the most significant induction of IFN-gamma mRNA, which also correlated with the dose of ionophore, inducing translocation of protein kinase C. This correlation between increased mRNA levels and protein kinase C translocation suggests that a calcium-dependent event is involved in induction of IFN-gamma mRNA synthesis. Furthermore, the magnitude of the translocation of protein kinase C from cytosol to plasma membrane corresponded to the physiologic IL 2 dose-response for IFN-gamma secretion. The data suggest that the activation of protein kinase C and/or coordinate elevation of intracellular calcium may provide at least one mechanism of signal transduction for the regulation of IFN-gamma gene transcription.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D004075:Diglycerides; D007376:Interleukin-2; D012333:RNA, Messenger; D000001:Calcimycin; D007371:Interferon-gamma; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate