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Published on: June 22, 2016
Xenon enhances LPS-induced IL-1β expression in microglia via the extracellular signal-regulated kinase 1/2 pathway
Astrid V Fahlenkamp1, Mark Coburn, Hajo Haase
1Department of Anaesthesiology, University Hospital Aachen, RWTH Aachen, Germany.
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% 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.
Insights
Xenon enhances immune cell cytokine production by activating ERK 1/2 signaling and reducing phosphatase activity. This study reveals xenon
Area of Science:
- Neuroimmunology
- Cellular Signaling
Background:
- Extracellular signal-regulated kinase (ERK) influences immune cell cytokine production.
- Microglia play a crucial role in neuroinflammation and immune responses.
Purpose of the Study:
- To investigate the effects of xenon on microglia phosphatase activity, ERK 1/2 signaling, and cytokine expression.
- To elucidate the mechanism by which xenon modulates immune responses in microglia.
Main Methods:
- Murine microglia cell line (BV-2) treated with lipopolysaccharide (LPS) and xenon.
- Analysis of cytokine levels using gene expression, Western blot, and ELISA.
- Assessment of phosphatase activity and ERK 1/2 phosphorylation, including inhibition studies with U0126.
Main Results:
- Xenon significantly enhanced LPS-induced interleukin-1 beta (IL-1β) expression.
- Xenon and LPS co-treatment led to increased ERK 1/2 phosphorylation, an effect inhibited by U0126.
- Xenon reduced microglia phosphatase activity by 20% and inhibited ERK 1/2 dephosphorylation.
- Blocking ERK 1/2 signaling attenuated the enhanced IL-1β expression.
Conclusions:
- Xenon enhances LPS-induced IL-1β expression in microglia primarily through the activation of ERK 1/2 signaling.
- Xenon's modulation of phosphatase activity is a key mechanism influencing intracellular signaling pathways in microglia.
- These findings suggest a potential role for xenon in modulating neuroinflammatory processes.
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