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Prostaglandin E2 (PGE2) stimulates the secretion of brain‐derived neurotrophic factor (BDNF) from cultured human microglia
Author(s) -
Hutchinson Anthony,
Chou ChihLing,
Israel Davelene,
Xu Wei,
Regan John W.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.729.4
Subject(s) - microglia , neurotrophin , neurotrophic factors , receptor , prostaglandin e2 , microbiology and biotechnology , prostaglandin e , prostaglandin e2 receptor , brain derived neurotrophic factor , biology , endocrinology , medicine , stimulation , central nervous system , chemistry , immunology , inflammation , agonist
PGE 2 is produced at high levels in the injured central nervous system (CNS), where it acts as a pro‐inflammatory mediator. The cellular actions of PGE 2 are mediated by G protein signaling pathways activated by receptors termed EP 1 , EP 2 , EP 3 and EP 4 . Recent animal studies indicate that PGE 2 also regulates the induction of growth factors that could participate in tissue repair after CNS injury. To examine the potential regulation of these factors by PGE 2 we obtained immortalized human microglial cells, which are the resident macrophages of the CNS. We analyzed PGE 2 ‐treated cultures using reverse transcriptase‐PCR, protein microarrays, ELISA, immunoblotting, and assays for both cyclic AMP production and reporter gene activity. We show that cultured human microglia express the mRNA for the EP 2 receptor, whereas the EP 1 , EP 3 and EP 4 mRNAs are not detected. Our data also demonstrate that PGE 2 stimulation promotes the secretion of BDNF, a neurotrophin growth factor that supports the survival of neurons. This induction of BDNF occurs in a time‐ and dose‐dependent manner through a cyclic AMP/protein kinase A pathway activated by the EP 2 receptor. These results suggest that endogenous PGE 2 , acting through the EP 2 receptor in microglia, may play a role in recovery from CNS injury via induction of BDNF release. Supported by EY11291.