Xenon enhances LPS-induced IL-1β expression in microglia via the extracellular signal-regulated kinase 1/2 pathway.
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.
Fahlenkamp
Astrid V
AV
Department of Anaesthesiology, University Hospital Aachen, RWTH Aachen, Germany.
Coburn
Mark
M
Haase
Hajo
H
Kipp
Markus
M
Ryang
Yu-Mi
YM
Rossaint
Rolf
R
Beyer
Cordian
C
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D053583:Interleukin-1beta / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014978:Xenon / Q000494:pharmacology*
D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014978:Xenon; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3