alexa Effects of extracellular pressure and alcohol on the microglial response to inflammatory stimulation.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Alcoholism & Drug Dependence

Author(s): Chaturvedi LS, Zhang P, Basson MD

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Abstract BACKGROUND: Traumatic brain injury induces a neuroinflammatory response frequently associated with increased intracranial pressure. The aim of this study was to investigate the effects of alcohol and increased extracellular pressure on murine BV-2 microglial proliferation and cytokine responses to lipopolysaccharide (LPS) stimulation. METHODS: BV-2 cells were cultured under 0 or 30 mm Hg increased extracellular pressure without or with ethanol (100 mmol/L) or LPS (10 ng/mL) for 24 hours. Cell proliferation was assessed using MTS assay and secretion of the proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-6, and monocyte chemotactic protein (MCP)-1 by enzyme-linked immunosorbent assay. RESULTS: Increased pressure and LPS stimulation each promoted proliferation. Ethanol pretreatment blocked these effects. Basal TNF-α and IL-6 secretion was at the limits of delectability. Basal MCP-1 production was stimulated by pressure, which was blocked by ethanol. Even this low LPS dose stimulated microglial secretion of TNF-α, IL-6, and MCP-1. Pressure inhibited LPS-stimulated production of these proinflammatory cytokines, while ethanol pretreatment blocked LPS-stimulated cytokine production. The combination of pressure and ethanol further reduced TNF-α, IL-6, and MCP-1 secretion by LPS-stimulated microglial cells. CONCLUSION: Alcohol's anti-inflammatory effects may contribute to the reduced mortality from traumatic brain injury that some have described in acutely intoxicated patients, while pressure down-regulation of inflammatory cytokine release could create a negative feedback that ameliorates inflammation in traumatic brain injury. Copyright © 2012 Elsevier Inc. All rights reserved.
This article was published in Am J Surg and referenced in Journal of Alcoholism & Drug Dependence

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