Selective modulation of BV-2 microglial activation by prostaglandin E2. Differential effects on endotoxin-stimulated cytokine induction

Tatiana V. Petrova, Keith T. Akama, Linda J. Van Eldik

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

The influence of prostaglandins on glial functions and, more specifically, on glial activation is not well understood. We report here that prostaglandin E2 (PGE2), one of the major prostaglandins produced in the brain, acts as a potent and selective inhibitor of tumor necrosis factor α (TNF-α) production in lipopolysaccharide-stimulated primary microglia and the microglial cell line BV-2. The IC50 for this effect is 1 nM, and 100 nM PGE2 suppresses TNF-α production by >95%. More detailed studies of BV-2 cells show that PGE2 also prevents the secretion of interleukin (IL)-6 but does not significantly modify lipopolysaccharide-stimulated expression of cyclooxygenase-2, pro-IL-1β, or inducible nitric oxide synthase. PGE2 appears to act primarily at the level of translation or protein stability, because TNF-α and IL-6 mRNA levels were only modestly decreased at high PGE2 concentrations; concomitantly with this inhibition, PGE2 up-regulated the levels of IL-1β mRNA. The effects of PGE2 could be largely mimicked by 8-bromo-cAMP, suggesting that, as in other cell types, PGE2 action is mediated at least in part by a rise in intracellular cyclic AMP. However, the protein kinase A inhibitor H89 only partially reversed the inhibition of TNF- α production by PGE2, implying that the PGE2 effect in BV-2 cells is mediated through both protein kinase A-dependent and -independent pathways.

Original languageEnglish
Pages (from-to)28823-28827
Number of pages5
JournalJournal of Biological Chemistry
Volume274
Issue number40
DOIs
StatePublished - Oct 1 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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