Abstract
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% O2 and 5% CO2. 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.
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Acknowledgements
We would like to thank J. Hoffmann and R. Blaumeiser-Debarry for their excellent technical assistance.
Declaration of Interests
Dr. Coburn and Prof. Dr. Rossaint received lecture and consultant fees from Air Liquide Santé International, a company interested in developing clinical applications for medical gases including xenon. None of the remaining authors received any corporate support, honoraria etc.
Funding
The study was supported by two grants allocated to A. Fahlenkamp (Forschungsrotation, START, both RWTH Aachen University).
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Fahlenkamp, A.V., Coburn, M., Haase, H. et al. Xenon Enhances LPS-Induced IL-1β Expression in Microglia via the Extracellular Signal-Regulated Kinase 1/2 Pathway. J Mol Neurosci 45, 48–59 (2011). https://doi.org/10.1007/s12031-010-9432-z
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DOI: https://doi.org/10.1007/s12031-010-9432-z