Oleamide suppresses lipopolysaccharide-induced expression of iNOS and COX-2 through inhibition of NF-kappaB activation in BV2 murine microglial cells

Neurosci Lett. 2010 May 3;474(3):148-153. doi: 10.1016/j.neulet.2010.03.026. Epub 2010 Mar 15.

Abstract

Oleamide (cis-9-octadecenamide) is an endogenous sleep-inducing fatty acid amide that accumulates in the cerebrospinal fluid of the sleep-deprived animals. Microglia are the major immune cells involved in neuroinflammation causing brain damage during infection, ischemia, and neurodegenerative disease. In this study, we examined the effects of oleamide on LPS-induced production of proinflammatory mediators and the mechanisms involved in BV2 microglia. Oleamide inhibited LPS-induced production of NO and prostaglandin E2 as well as expression of iNOS and COX-2. We showed that oleamide blocked LPS-induced NF-kappaB activation and phosphorylation of inhibitor kappaB kinase (IKK). We also showed that oleamide inhibited LPS-induced phosphorylation of Akt, p38 MAPK, and ERK, activation of PI 3-kinase, and accumulation of reactive oxygen species (ROS). Finally, we showed that a specific antagonist of the CB2 receptor, AM630, blocked the inhibitory effects of oleamide on LPS-induced production of proinflammatory mediators and activation of NF-kappaB. Taken together, our results suggest that oleamide shows an anti-inflammatory effect through inhibition of NF-kappaB activation in LPS-stimulated BV2 microglia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Separation
  • Cyclooxygenase 2 / biosynthesis*
  • Enzyme Activation / physiology
  • Flow Cytometry
  • Gene Expression
  • Immunoblotting
  • Immunoprecipitation
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / pharmacology
  • Mice
  • Microglia / metabolism*
  • NF-kappa B / metabolism*
  • Nitric Oxide Synthase Type II / biosynthesis*
  • Oleic Acids / metabolism*
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • Oleic Acids
  • RNA, Messenger
  • oleylamide
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2