Cyclooxygenase-2 contributes to oxidopamine-mediated neuronal inflammation and injury via the prostaglandin E2 receptor EP2 subtype

Cyclooxygenase-2 (COX-2) triggers pro-inflammatory processes that can aggravate neuronal degeneration and functional impairments in many neurological conditions, mainly via producing prostaglandin E2 (PGE 2 ) that activates four membrane receptors, EP1-EP4. However, which EP receptor is the culprit...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Scientific reports 2017-08, Vol.7 (1), p.9459-14, Article 9459
Hauptverfasser: Kang, Xu, Qiu, Jiange, Li, Qianqian, Bell, Katherine A., Du, Yifeng, Jung, Da Woon, Lee, Jae Yeol, Hao, Jiukuan, Jiang, Jianxiong
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Cyclooxygenase-2 (COX-2) triggers pro-inflammatory processes that can aggravate neuronal degeneration and functional impairments in many neurological conditions, mainly via producing prostaglandin E2 (PGE 2 ) that activates four membrane receptors, EP1-EP4. However, which EP receptor is the culprit of COX-2/PGE 2 -mediated neuronal inflammation and degeneration remains largely unclear and presumably depends on the insult types and responding components. Herein, we demonstrated that COX-2 was induced and showed nuclear translocation in two neuronal cell lines – mouse Neuro-2a and human SH-SY5Y – after treatment with neurotoxin 6-hydroxydopamine (6-OHDA), leading to the biosynthesis of PGE 2 and upregulation of pro-inflammatory cytokine interleukin-1β. Inhibiting COX-2 or microsomal prostaglandin E synthase-1 suppressed the 6-OHDA-triggered PGE 2 production in these cells. Treatment with PGE 2 or EP2 selective agonist butaprost, but not EP4 agonist CAY10598, increased cAMP response in both cell lines. PGE 2 -initiated cAMP production in these cells was blocked by our recently developed novel selective EP2 antagonists – TG4-155 and TG6-10-1, but not by EP4 selective antagonist GW627368X. The 6-OHDA-promoted cytotoxicity was largely blocked by TG4-155, TG6-10-1 or COX-2 selective inhibitor celecoxib, but not by GW627368X. Our results suggest that PGE 2 receptor EP2 is a key mediator of COX-2 activity-initiated cAMP signaling in Neuro-2a and SH-SY5Y cells following 6-OHDA treatment, and contributes to oxidopamine-mediated neurotoxicity.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-09528-z