Synergistic activation of lipopolysaccharide-stimulated glial cells by propofol

Biochem Biophys Res Commun. 2013 Aug 23;438(2):420-6. doi: 10.1016/j.bbrc.2013.07.089. Epub 2013 Jul 27.

Abstract

Despite the extensive use of propofol in general anesthetic procedures, the effects of propofol on glial cell were not completely understood. In lipopolysaccharide (LPS)-stimulated rat primary astrocytes and BV2 microglial cell lines, co-treatment of propofol synergistically induced inflammatory activation as evidenced by the increased production of NO, ROS and expression of iNOS, MMP-9 and several cytokines. Propofol augmented the activation of JNK and p38 MAPKs induced by LPS and the synergistic activation of glial cells by propofol was prevented by pretreatment of JNK and p38 inhibitors. When we treated BV2 cell culture supernatants treated with LPS plus propofol on cultured rat primary neuron, it induced a significant neuronal cell death. The results suggest that the repeated use of propofol in immunologically challenged situation may induce glial activation in brain.

Keywords: Cytokines; JNK; Neuronal death; iNOS; p38.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Intravenous / pharmacology
  • Animals
  • Astrocytes / cytology
  • Cell Death
  • Cell Survival
  • Cells, Cultured
  • Cerebral Cortex / metabolism
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / metabolism*
  • MAP Kinase Kinase 4 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Neuroglia / cytology*
  • Neuroglia / drug effects*
  • Neurons / cytology
  • Neurons / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Propofol / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anesthetics, Intravenous
  • Cytokines
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • Reactive Oxygen Species
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat
  • Propofol