Prostaglandin E2potentiates interferon-γ-induced nitric oxide production in cultured rat microglia
| Autor: | Daisuke Yamanaka, Ryo Nishiyama, Satoshi Kishimoto, Yukiko Mutaguchi, Takayuki Nagano, Hirohisa Umeki, Anna Ioku, Ayaka Sanada, Shinya H. Kimura, Motohiko Takemura |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Agonist biology Chemistry medicine.drug_class Prostaglandin E2 receptor Antagonist Pharmacology Biochemistry Nitric oxide Nitric oxide synthase 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 030104 developmental biology biology.protein medicine lipids (amino acids peptides and proteins) Cyclic adenosine monophosphate Nitrite Prostaglandin E2 medicine.drug |
| Zdroj: | Journal of Neurochemistry. 140:605-612 |
| ISSN: | 0022-3042 0441-8948 |
| Popis: | Prostaglandin E2 (PGE2 ) plays crucial roles in managing microglial activation through the prostanoid EP2 receptor, a PGE2 receptor subtype. In this study, we report that PGE2 enhances interferon-γ (IFN-γ)-induced nitric oxide production in microglia. IFN-γ increased the release of nitrite, a metabolite of nitric oxide, which was augmented by PGE2 , although PGE2 by itself slightly affects nitrite release. The potentiating effect of PGE2 was positively associated with increased expression of inducible nitric oxide synthase. In contrast to nitrite release induced by IFN-γ, lipopolysaccharide-induced nitrite release was not affected by PGE2 . An EP2 agonist, ONO-AE1-259-01 also augmented IFN-γ-induced nitrite release, while an EP1 agonist, ONO-DI-004, an EP3 agonist, ONO-AE-248, or an EP4 agonist, ONO-AE1-329, did not. In addition, the potentiating effect of PGE2 was 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. Among the EP agonists, ONO-AE1-259-01 alone was able to accumulate cyclic adenosine monophosphate (AMP), and among the EP antagonists, PF-04418948 was the only one able to inhibit PGE2 -increased intracellular cyclic AMP accumulation. On the other hand, IFN-γ promoted phosphorylation of signal transducer and activator of transcription 1, which was not affected by PGE2 . Furthermore, other prostanoid receptor agonists, PGD2 , PGF2α , iloprost, and U-46119, slightly affected IFN-γ-induced nitrite release. These results indicate that PGE2 potentiates IFN-γ-induced nitric oxide production in microglia through the EP2 receptor, which may shed light on one of the pro-inflammatory aspects of PGE2 . |
| Databáze: | OpenAIRE |
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