Prostaglandin E₂ (PGE₂) plays an important role in modulating microglial function. In the present study, we have found that PGE2 increases protein of cyclooxygenase-2 (COX-2), which are involved in PGE₂ synthase in cultured rat microglia.
COX-2 protein was increased by PGE₂ at 10^-6 M for 3 h in microglia. The increase was inhibited by PF-04418948 (EP₂ antagonist), but not by ONO-8713 (EP₁ antagonist), ONO-AE3-240 (EP₃ antagonist), or ONO-AE3-208 (EP₄ antagonist) at 10^-6 M. In addition, ONO-AE1-259-01 (EP₂ agonist), also increased COX-2 protein in a dose dependent manner, and this protein level was not affected by ONO-DI-004 (EP₁ agonist), ONO-AE-248 (EP₃ agonist), or ONO-AE1-329 (EP₄ agonist) at 10^-6 M. Moreover, PGE₂ at 10^-6 M for 3 h had little effect on the protein expression of cyclooxygenase-1, microsomal prostaglandin E synthase-1, microsomal prostaglandin E synthase-2, or cytosolic prostaglandin E synthase, which are also involved in PGE₂ synthase.
Therefore, activation of EP₂ receptor results in the increase of COX-2 protein in microglia.