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 Citations (Scopus)

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

Fingerprint

Platelet Activating Factor
Tumor Necrosis Factor-alpha
Dinoprostone
Budesonide
Free Radical Scavengers
Brain Death
Prostaglandin-Endoperoxide Synthases
Phosphatidylcholines
Brain Injuries
Transcriptional Activation
Glucocorticoids
Genes
Cell Survival
Oxidative Stress
Cell Death
Up-Regulation
Electrons
Apoptosis
Gene Expression

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)

Cite this

Synergism in the repression of COX-2- and TNFα-induction in platelet activating factor-stressed human neural cells. / Boetkjaer, Anja; Boedker, Merete; Cui, Jian Guo; Zhao, Yuhai; Lukiw, Walter J.

In: Neuroscience Letters, Vol. 426, No. 1, 09.10.2007, p. 59-63.

Research output: Contribution to journalArticle

Boetkjaer, Anja ; Boedker, Merete ; Cui, Jian Guo ; Zhao, Yuhai ; Lukiw, Walter J. / Synergism in the repression of COX-2- and TNFα-induction in platelet activating factor-stressed human neural cells. In: Neuroscience Letters. 2007 ; Vol. 426, No. 1. pp. 59-63.
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