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

Abstract We have analyzed the effect mediated by prostaglandin E 2 (PGE 2 ) and different reagents that increase intracellular cAMP on the expression of the p55 subunit (CD25) of interleukin 2 receptors (IL2R), 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 PGE 2 (10 −6 M ), forskolin (5 × 10 −5 M ), cholera toxin (0.2 μg/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 IL2R, detectable after 24 h. Furthermore, it was observed that PGE 2 reduced the concentration of IL2R‐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 IL2 only partially reversed the inhibition, thus suggesting that PGE 2 and increased intracellular concentration of cAMP directly interfered with CD25 expression and that their effect could not be merely attributed to a lack of IL2 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 PGE 2 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 IL2R.