Xenon enhances LPS-induced IL-1β expression in microglia via the extracellular signal-regulated kinase 1/2 pathway

J Mol Neurosci. 2011 Sep;45(1):48-59. doi: 10.1007/s12031-010-9432-z. Epub 2010 Aug 3.


The extracellular signal-regulated kinase (ERK) is involved in the cytokine production of immune cells. In this study, we show the influence of xenon on phosphatase activity, ERK 1/2 signalling and cytokine expression in microglia. The murine microglia cell line BV-2 was treated with 50 ng/ml lipopolysaccharide (LPS) and 74% xenon in 21% O(2) and 5% CO(2). Cytokine levels were examined by gene expression analysis, Western blot and enzyme-linked immunosorbent assay. Phosphatase inhibition was assessed with p-nitrophenylphosphate and phosphorylation of ERK 1/2 via Western blot. Xenon significantly enhanced LPS-mediated IL-1β expression. ERK 1/2 phosphorylation was observed after xenon or LPS treatment which was inhibited by the use of the MEK inhibitor U0126. Xenon and LPS in combination superimposed individual effects on ERK 1/2 activation. Xenon decreased cellular phosphatase activity in microglia by 20% and inhibited dephosphorylation of ERK 1/2 up to 1 h. The blocking of ERK 1/2 reduced IL-1β expression in xenon and LPS-treated cells to a level obtained by LPS alone. In conclusion, xenon enhanced LPS-induced IL-1β expression in microglia by activation of ERK 1/2 signalling. Xenon's interference with phosphatases may be a key feature to affect multiple intracellular signalling pathways.

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Interleukin-1beta / metabolism*
  • Lipopolysaccharides / pharmacology*
  • Mice
  • Microglia / cytology
  • Microglia / drug effects*
  • Microglia / metabolism*
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Signal Transduction / drug effects
  • Xenon / pharmacology*


  • Interleukin-1beta
  • Lipopolysaccharides
  • Xenon
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3