Exclusive expression of the Gs-linked prostaglandin E(2) receptor subtype 4 mRNA in human mononuclear Jurkat and KM-3 cells and coexpression of subtype 4 and 2 mRNA in U-937 cells

Prostaglandin E(2) (PGE(2)) is regarded as a potent regulator of the immune system, It can regulate apoptosis in mononuclear cells and modulate the cytokine secretion pattern from T-helper cell subpopulations via an increase in cyclic AMP (cAMP), Of the 4 PGE(2) receptor subtypes (EP1-EP4) that are defined pharmacologically by their affinity to subtype-specific ligands and their coupling to G proteins, EP2 and EP4 receptors couple to Gs. It is as yet unknown which of these two receptor subtypes mediates the immunomodulatory effects, By quantitative RT-PCR, the mRNA for EP4 receptors was demonstrated and quantified in the human mononuclear cell lines Jurkat, KM-3 and U-937, However, EP2 receptor mRNA was only present in U-937 cells and was 100-fold less abundant than EP4 receptor mRNA, PGE(2) increased cAMP formation with an ED(50) of 50-100 nM in all cell lines, cAMP formation was inhibited by the EP4R-specific antagonist AH23848, Since AH23848 inhibited PGE(2)-induced cAMP formation in U-937 cells to a similar extent as in Jurkat and KM-3, EP2 receptors seem to play, if any, only a secondary role for the PGE(2)-mediated cAMP formation in U-937 cells.