Activation of EP2 prostanoid receptors in human glial cell lines stimulates the secretion of BDNF

Anthony J. Hutchinson, Chih Ling Chou, Davelene D. Israel, Wei Xu, John W. Regan

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Prostaglandin E2 (PGE2) is produced at high levels in the injured central nervous system, where it is generally considered a cytotoxic mediator of inflammation. The cellular actions of PGE2 are mediated by G-protein signaling activated by prostanoid receptors termed EP1, EP2, EP3 and EP4. Recent studies have implicated the EP2 prostanoid receptor to be in apparently conflicting roles promoting neuronal death in some model systems and the survival of neurons in others. Here we show that treatment of immortalized human microglia and CCF-STTG1 astrocytes with either PGE2 or the EP2 selective agonist butaprost stimulates the release of brain-derived neurotrophic factor (BDNF). Both cell lines express mRNA for the EP2 receptor, whereas transcripts for the other subtypes are not detected. Pharmacological studies using PGE2 and modulators of cyclic AMP signaling implicate this pathway in PGE2-stimulated BDNF release. These results indicate that EP2 prostanoid receptor activation induces BDNF secretion through stimulation of cyclic AMP dependent signaling. Our findings provide a mechanism by which endogenous PGE2 might contribute to either neurotoxicity or neuroprotection in the injured brain via the induction of BDNF release from microglial cells and astrocytes.

Original languageEnglish (US)
Pages (from-to)439-446
Number of pages8
JournalNeurochemistry International
Volume54
Issue number7
DOIs
StatePublished - Jun 1 2009

Keywords

  • Astrocytes
  • BDNF
  • Brain-derived neurotrophic factor
  • Cyclic AMP
  • G-protein coupled receptor
  • Microglia
  • Prostaglandin E

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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