GliaDec 12, 2017

Activation of EP2 receptor reduces inflammation caused by viral and bacterial signals in brain immune cells and tissue, involving MAPK pathways

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 31, 2026

Abstract

Prostaglandin E receptor 2 (EP) activation may reduce inflammatory responses in microglia during neuroinflammation.

Brain inflammation is associated with neurodegenerative diseases.
Depletion of microglia altered the expression of TLR3 and TLR4 receptors in organotypic hippocampal slice cultures (OHSCs).
Poly(I:C) stimulation increased the production of prostaglandin E in OHSCs by enhancing the activity of cyclooxygenase (COX-2) and microsomal prostaglandin E synthase (mPGES)-1.
Co-stimulation with the EP agonist butaprost reduced inflammatory mediators induced by LPS and Poly(I:C) in microglia and OHSCs.
Butaprost treatment improved microglial morphology and decreased Iba1 immunoreactivity in Poly(I:C)-challenged OHSCs.
Activation of EP reversed the phosphorylation of MAPKs (ERK, p38 MAPK, and JNK) in microglia during inflammatory challenges.

Simplified

Brain inflammation is a critical factor involved in neurodegeneration. Recently, the prostaglandin E(PGE) downstream members were suggested to modulate neuroinflammatory responses accompanying neurodegenerative diseases. In this study, we investigated the protective effects of prostaglandin Ereceptor 2 (EP) during TLR3 and TLR4-driven inflammatory response using in vitro primary microglia and ex vivo organotypic hippocampal slice cultures (OHSCs). Depletion of microglia from OHSCs differentially affected TLR3 and TLR4 receptor expression. Poly(I:C) induced the production of prostaglandin Ein OHSCs by increasing cyclooxygenase (COX-2) and microsomal prostaglandin E synthase (mPGES)-1. Besides, stimulation of OHSCs and microglia with Poly(I:C) upregulated EPreceptor expression. Co-stimulation of OHSCs and microglia with the EPagonist butaprost reduced inflammatory mediators induced by LPS and Poly(I:C). In Poly(I:C) challenged OHSCs, butaprost almost restored microglia ramified morphology and reduced Iba1 immunoreactivity. Importantly, microglia depletion prevented the induction of inflammatory mediators following Poly(I:C) or LPS challenge in OHSCs. Activation of EPreceptor reversed the Poly(I:C)/LPS-induced phosphorylation of the mitogen activated protein kinases (MAPKs) ERK, p38 MAPK and c-Jun N-terminal kinase (JNK) in microglia. Collectively, these data identify an anti-inflammatory function for EPsignaling in diverse innate immune responses, through a mechanism that involves the mitogen-activated protein kinases pathway. 2 2 2 2 2 2 2 2 2

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Activation of EP2 receptor reduces inflammation caused by viral and bacterial signals in brain immune cells and tissue, involving MAPK pathways

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