Prostaglandin E increases the expression of cyclooxygenase-2 in cultured rat microglia.

Prostaglandin E (PGE) plays pivotal roles in controlling microglial activation with the EP receptor, a PGE receptor subtype. Activated microglia are often reported to increase cyclooxygenase (COX)-2 expression, followed by PGE production, but it is unclear whether extracellular PGE is involved in microglial PGE synthesis. In the present study, we report that PGE increases COX-2 protein in microglia. In a culture system, PGE at 10 M for 3 h increased COX-2 and microsomal PGE synthase (mPGES)-1 mRNA levels, and reduced mPGES-2, but did not affect COX-1 or cytosolic PGE synthase (cPGES) in microglia. PGE at 10 M for 3 h also increased the COX-2 protein level, but did not affect COX-1, mPGES-1, mPGES-2, or cPGES. An EP agonist, ONO-AE1-259-01, also increased COX-2 and mPGES-1 mRNA levels, and reduced mPGES-2, but did not affect COX-1 or cPGES, whereas an EP agonist, ONO-DI-004, an EP agonist, ONO-AE-248, and an EP agonist, ONO-AE1-329, had no effect. Similar to PGE, ONO-AE1-259-01 increased the COX-2 protein level, but did not affect COX-1, mPGES-1, mPGES-2, or cPGES. In addition, the effects of PGE were inhibited by an EP antagonist, PF-04418948, but not by an EP antagonist, ONO-8713, an EP antagonist, ONO-AE3-240, or an EP antagonist, ONO-AE3-208, at 10 M. On the other hand, lipopolysaccharide (LPS) increased PGE production, but the LPS-induced PGE production was not affected by ONO-8713, PF-04418948, ONO-AE3-240, or ONO-AE3-208. These results indicate that PGE increases COX-2 protein in microglia through the EP receptor supporting the idea that extracellular PGE has a triggering aspect for microglial activation.