In:
Journal of Neurochemistry, Wiley, Vol. 140, No. 4 ( 2017-02), p. 605-612
Abstract:
Prostaglandin E 2 (PGE 2 ) plays crucial roles in managing microglial activation through the prostanoid EP 2 receptor, a PGE 2 receptor subtype. In this study, we report that PGE 2 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 PGE 2 , although PGE 2 by itself slightly affects nitrite release. The potentiating effect of PGE 2 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 PGE 2 . An EP 2 agonist, ONO‐AE1‐259‐01 also augmented IFN‐γ‐induced nitrite release, while an EP 1 agonist, ONO‐DI‐004, an EP 3 agonist, ONO‐AE‐248, or an EP 4 agonist, ONO‐AE1‐329, did not. In addition, the potentiating effect of PGE 2 was inhibited by an EP 2 antagonist, PF‐04418948, but not by an EP 1 antagonist, ONO‐8713, an EP 3 antagonist, ONO‐AE3‐240, or an EP 4 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 PGE 2 ‐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 PGE 2 . Furthermore, other prostanoid receptor agonists, PGD 2 , PGF 2α , iloprost, and U‐46119, slightly affected IFN‐γ‐induced nitrite release. These results indicate that PGE 2 potentiates IFN‐γ‐induced nitric oxide production in microglia through the EP 2 receptor, which may shed light on one of the pro‐inflammatory aspects of PGE 2 . image
Type of Medium:
Online Resource
ISSN:
0022-3042
,
1471-4159
DOI:
10.1111/jnc.2017.140.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2020528-4
SSG:
12
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