Prostaglandin E2 and the increase of intracellular cAMP inhibit the expression of interleukin 2 receptors in human T cells.

We have analyzed the effect mediated by prostaglandin E2 (PGE2) and different reagents that increase intracellular cAMP on the expression of the p55 subunit (CD25) of interleukin 2 receptors (IL 2R), on the levels of CD25-specific mRNA and on the expression of high affinity IL 2R. In purified T cells, activated either by an anti-CD3 monoclonal antibody or phytohemagglutinin, the addition of PGE2 (10(-6) M), forskolin (5 X 10(-5) M), cholera toxin (0.2 microgram/ml) or dibutyryl cAMP (dBcAMP) (10(-4) M) decreased the cell surface expression of IL 2R by reducing (40%-78% inhibition) the proportions of CD25+ cells as well as the expression of high affinity IL 2R, detectable after 24 h. Furthermore, it was observed that PGE2 reduced the concentration of IL 2R-specific mRNA after a 6-h period of activation, indicating that its regulatory activity takes place at a pretranslational level. The addition of exogenous recombinant IL 2 only partially reversed the inhibition, thus suggesting that PGE2 and increased intracellular concentration of cAMP directly interfered with CD25 expression and that their effect could not be merely attributed to a lack of IL 2-dependent positive feedback. Cells cultured under the same conditions in the presence of phorbol myristate acetate, that activates protein kinase C, were refractory to the cAMP-mediated regulation. Finally, we demonstrate that both PGE2 and dBcAMP inhibit the generation of inositol metabolites after T cell activation, thus indicating that these reagents interfere with early signal transduction mechanisms which precede the synthesis of IL 2R.