Regulation of interleukin 2 synthesis by cAMP in human T cells.
T cell activation requires two initial signals that first lead to the expression of interleukin 2 (IL 2) receptors and the initiation of IL 2 synthesis and then to T cell proliferation. Jurkat T lymphoma cells have been shown to be a good model for studying IL 2 synthesis because these cells also require two signals for activation. The first signal can be provided by the lectin phytohaemagglutinin (PHA), and the second one by the phorbol ester, 12-o-tetradecanoylphorbol 13-acetate (TPA). The regulation of IL 2 synthesis in Jurkat cells, however, is unclear, and the present study deals with the role of cAMP on IL 2 synthesis. In Jurkat cells, IL 2 synthesis appears to be highly regulated by the activity of adenylate cyclase. This was demonstrated by using different means to increase intracellular cAMP level, namely by using permeant cAMP analogs, using the activator of adenylate cyclase, forskolin, using the activator of the alpha subunit of the stimulatory GTP binding protein cholera toxin, and using inhibitors of phosphodiesterase. In addition, prostaglandins E1 and E2 were shown to bind specifically to Jurkat cells, to induce a rise in intracellular cAMP level, and to markedly decrease IL 2 synthesis. All together, these results suggest that in T lymphocytes, the prostaglandin E2 receptor is linked to adenylate cyclase through a GTP binding protein and regulates the production of IL 2 by controlling the intracellular cAMP level.
D000262:Adenylyl Cyclases / Q000502:physiology; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D015232:Dinoprostone; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D013601:T-Lymphocytes / Q000502:physiology*
D007376:Interleukin-2; D010726:Phosphodiesterase Inhibitors; D011458:Prostaglandins E; D003994:Bucladesine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015232:Dinoprostone