S. aureus-dependent microglial activation is selectively attenuated by the cyclopentenone prostaglandin 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2)

Tammy Kielian, Meredith McMahon, Edward D. Bearden, Aaron C. Baldwin, Paul D. Drew, Nilufer Esen

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Microglial activation is a hallmark of brain abscess. The continual release of proinflammatory mediators by microglia following bacterial challenge may contribute, in part, to the destruction of surrounding normal tissue characteristic of brain abscess. Therefore, attenuating chronic microglial activation during the course of CNS bacterial infections may have therapeutic benefits. The purpose of this study was to evaluate the ability of the natural peroxisome proliferator-activated receptor (PPAR)-γ agonist 15-deoxy-Δ12,14- prostaglandin J2 (15d-PGJ2) to modulate microglial activation in response to Staphylococcus aureus, one of the main etiologic agents of brain abscess in humans. 15d-PGJ2 was a potent inhibitor of proinflammatory cytokine (IL-1β, TNF-α, IL-12 p40) and CC chemokine (MIP-1β, MCP-1) production in primary microglia, but had no effect upon the expression of select CXC chemokines (MIP-2, KC). 15d-PGJ2 also selectively inhibited the S. aureus-dependent increase in microglial TLR2, CD14, MHC class II, and CD40 expression, whereas it had no effect on the co-stimulatory molecules CD80 and CD86. Microarray analysis revealed additional inflammatory mediators modulated by 15d-PGJ2 in primary microglia following S. aureus exposure, the majority of which were chemokines. These results suggest that suppressing microglial activation through the use of 15d-PGJ2 may lead to the sparing of damage to normal brain parenchyma that often results from brain abscess.

Original languageEnglish (US)
Pages (from-to)1163-1172
Number of pages10
JournalJournal of Neurochemistry
Volume90
Issue number5
DOIs
StatePublished - Sep 1 2004

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Keywords

  • 15d-PGJ2
  • Chemokines
  • Cytokines
  • Microglia
  • PPAR-γ
  • Staphylococcus aureus

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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