Differential effects of ethanol on glial signal transduction initiated by lipopolysaccharide and interferon‐γ

Abstract

Although the pathogenic effects of alcohol abuse on brain are well established, its specific effects on the intracellular signal transduction pathways of glial cells in the central nervous system (CNS) are poorly understood. In this study, we evaluated how ethanol affects the glial signal transduction associated with inflammatory activation. Lipopolysaccharide (LPS), gangliosides, and interferon (IFN)‐γ induced the inflammatory activation of glia, which was differentially influenced by ethanol: 1) ethanol inhibited LPS‐ or gangliosides‐induced, but not IFNγ‐induced, glial activation as demonstrated by the production of nitric oxide and the expression of inflammatory genes such as interleukin‐1β, tumor necrosis factor‐α, IP‐10, and CD86; 2) nuclear factor (NF)‐κB or JAK/STAT1 pathway was necessary for LPS‐ or IFNγ‐induced glial activation, respectively; 3) ethanol inhibited LPS‐induced NF‐κB activation; and 4) ethanol did not significantly affect IFNγ‐induced STAT1/IRF‐1 activation. Based on these results, ethanol seems to inhibit selectively some parts of the glial signal transduction pathways that are associated with inflammatory activation, which may lead to the deregulation of CNS inflammatory responses.