Analysis of prostaglandin E2 effect on T lymphocyte activation. Abrogation of prostaglandin E2 inhibitory effect by the tumor promotor 12.0 tetradecanoyl phorbol-13 acetate.
We have investigated the inhibitory potential of prostaglandin E2 (PGE2) with respect to intracellular messengers implicated in the signaling system of T-lymphocyte activation pathway. Using the fluorescent indicator Quin 2, it is demonstrated that PGE2 inhibits the increase in cytosolic-free calcium concentration [Ca2+]i. Reconstitution of calcium mobilization in the presence of PGE2 by the calcium ionophore A23187 results in a partial restoration of both interleukin 2 (IL2) production and cell proliferation and has no effect on the inhibition of transferrin receptor expression. In contrast, the treatment of cell cultures with the tumor promotor 12.0 tetra decanoyl phorbol-13-acetate (TPA) abrogates the suppressor activity of PGE2. When T lymphocyte stimulation is provided by the combination of A23187 and TPA, the PGE2 inhibitory effect does not occur. These data also indicate that the down regulation of transferrin receptor by PGE2 is proximal to protein kinase C activation and is not associated with decreased expression of the functional IL2 receptor.
D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D003593:Cytoplasm / Q000502:physiology; D015232:Dinoprostone; D004789:Enzyme Activation; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects*; D011458:Prostaglandins E / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007376:Interleukin-2; D011458:Prostaglandins E; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D000001:Calcimycin; D000242:Cyclic AMP; D011493:Protein Kinase C; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium