Ketamine suppresses endotoxin-induced NF-κB expression

T. Sakai, T. Ichiyama, C. W. Whitten, A. H. Giesecke, J. M. Lipton

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Purpose: Ketamine reduces endotoxin-induced production of proinflammatory cytokines, including tumour necrosis factor- α (TNF), in several types of inflammatory cells, including monocytes and macrophages. Transcription of the genes that encode production of these proinflammatory cytokines is regulated by nuclear factor-kappa B (NF-κB). Cytoplasmic B protein is activated by endotoxin (LPS) as well as by TNF, allowing B protein to migrate into the cell nucleus to activate gene transcription for these inflammatory mediators. Because NF-κB is likely involved in brain injury and inflammatory neurodegenerative disease, such as multiple sclerosis, we examined whether ketamine inhibits LPS-induced activation of NF-κB in human glioma cells in vitro and intact mouse brain cells in viva. Methods: Endotoxin-induced NF-κB expression in both the human glioma cells in vitro and the intact mouse brain cells in viva was determined by electrophoretic mobility shift assays (EMSA) of nuclear extracts and measurement of NF-κB expression by densitometry. Endotoxin was injected intracerebroventricularly in viva and intact brain was harvested. Klenow fragment labeling was used to identify NF-κB protein for both the in viva and vitro experiments. Results: Endotoxin treatment increased NF-κB expression (P < 0.05) both in viva and vitro compared with control (untreated) cells. Ketamine suppressed endotoxin-induced neuronal NF-κB activation in a dose-dependent manner (P < 0.05, except for the 10-5M concentration in vitro) both in viva and vitro. Conclusion: Ketamine inhibits endotoxin-induced NF-κB expression in brain cells in viva and vitro and it is suggested that this may have implications in the neuroprotective effects of ketamine reported by other investigators.

Original languageEnglish (US)
Pages (from-to)1019-1024
Number of pages6
JournalCanadian Journal of Anesthesia
Volume47
Issue number10
DOIs
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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