Synergism in the repression of COX-2- and TNFα-induction in platelet activating factor-stressed human neural cells

Anja Boetkjaer, Merete Boedker, Jian Guo Cui, Yuhai Zhao, Walter J. Lukiw

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Platelet activating factor (PAF; β-acetyl-γ-O-hexadecyl-l-α-phosphatidylcholine) triggers a rapid pro-inflammatory gene expression program in primary cultures of human neural (HN) cells. Two genes and gene products consistently induced after PAF treatment are the cytosoluble prostaglandin synthase cycloooxygenase-2 (COX-2) and the pro-apoptotic tumor necrosis factor alpha (TNFα). Both of these mediators are associated with the activation of inflammatory signaling, neural cell dysfunction, apoptosis and brain cell death, and both have been found to be up-regulated after brain injury in vivo. In this study we investigated the effects of the non-halogenated synthetic glucocorticoid budesonide epimer R (BUDeR), the novel PAF antagonist LAU-0901, and the electron spin trap and free radical scavenger phenyl butyl nitrone (PBN), upon early COX-2 and TNFα gene activation and prostaglandin E2 (PGE2) release in PAF-stressed primary HN cells. The data indicate that these three biochemically unrelated classes of inflammatory repressors act synergistically in modulating PAF-induced up-regulation of COX-2, TNFα, and PGE2 by quenching oxidative stress or inflammatory signaling, resulting in increased HN cell survival. These, or analogous classes of compounds, may be useful in the design of more effective combinatorial pharmacotherapeutic strategies in the treatment of complex neuro-inflammatory disorders.

Original languageEnglish (US)
Pages (from-to)59-63
Number of pages5
JournalNeuroscience Letters
Volume426
Issue number1
DOIs
StatePublished - Oct 9 2007

Keywords

  • Budesonide epimer R
  • Cyclooxygenase-2
  • Human neural cells
  • LAU-0901
  • Neuroinflammation
  • Oxidative stress
  • Phenyl butyl nitrone
  • Prostaglandin E
  • TNFα

ASJC Scopus subject areas

  • Neuroscience(all)

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