Differential effects of ethanol on glial signal transduction initiated by lipopolysaccharide and interferon-gamma.
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)-gamma induced the inflammatory activation of glia, which was differentially influenced by ethanol: 1) ethanol inhibited LPS- or gangliosides-induced, but not IFNgamma-induced, glial activation as demonstrated by the production of nitric oxide and the expression of inflammatory genes such as interleukin-1beta, tumor necrosis factor-alpha, IP-10, and CD86; 2) nuclear factor (NF)-kappaB or JAK/STAT1 pathway was necessary for LPS- or IFNgamma-induced glial activation, respectively; 3) ethanol inhibited LPS-induced NF-kappaB activation; and 4) ethanol did not significantly affect IFNgamma-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.
Choi
Dong-Kug
DK
Department of Biotechnology, Konkuk University, Chungju, Korea.
Lee
Heasuk
H
Jeong
Jaeyoon
J
Lim
Beongou
B
Suk
Kyoungho
K
D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions / Q000502:physiology; D004660:Encephalitis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D000431:Ethanol / Q000494:pharmacology*; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology; D005732:Gangliosides / Q000037:antagonists & inhibitors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D002492:Central Nervous System Depressants; D016207:Cytokines; D005732:Gangliosides; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D050794:STAT1 Transcription Factor; D000431:Ethanol; D007371:Interferon-gamma