Prostaglandin E2 increases the expression of cyclooxygenase-2 in cultured rat microglia

• Published in: Journal of neuroimmunology 2021-12, Vol.361, p.577724-577724, Article 577724
• Main Authors: Nagano, Takayuki, Tsuda, Naohiko, Fujimura, Kenichi, Ikezawa, Yuji, Higashi, Yuki, Kimura, Shinya H.
• Format: Article
• Language: English
• Subjects: Microglia; PGE2; Ptger2; Ptges; Ptgs2
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2021.577724

Prostaglandin E2 (PGE2) plays pivotal roles in controlling microglial activation with the EP2 receptor, a PGE2 receptor subtype. Activated microglia are often reported to increase cyclooxygenase (COX)-2 expression, followed by PGE2 production, but it is unclear whether extracellular PGE2 is involved in microglial PGE2 synthesis. In the present study, we report that PGE2 increases COX-2 protein in microglia. In a culture system, PGE2 at 10−6 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. PGE2 at 10−6 M for 3 h also increased the COX-2 protein level, but did not affect COX-1, mPGES-1, mPGES-2, or cPGES. An EP2 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 EP1 agonist, ONO-DI-004, an EP3 agonist, ONO-AE-248, and an EP4 agonist, ONO-AE1-329, had no effect. Similar to PGE2, 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 PGE2 were inhibited by an EP2 antagonist, PF-04418948, but not by an EP1 antagonist, ONO-8713, an EP3 antagonist, ONO-AE3‐240, or an EP4 antagonist, ONO-AE3‐208, at 10−6 M. On the other hand, lipopolysaccharide (LPS) increased PGE2 production, but the LPS-induced PGE2 production was not affected by ONO-8713, PF-04418948, ONO-AE3‐240, or ONO-AE3‐208. These results indicate that PGE2 increases COX-2 protein in microglia through the EP2 receptor supporting the idea that extracellular PGE2 has a triggering aspect for microglial activation. [Display omitted] •Prostaglandin E2 increases cyclooxygenase-2 protein in microglia.•An EP2 agonist, ONO-AE1-259-01, increases cyclooxygenase-2 protein in microglia.•An EP2 antagonist, PF-04418948, inhibits prostaglandin E2-induced cyclooxygenase-2 protein expression in microglia.