Ethanol increases nuclear factor-kappa B activity in human astroglial cells.
Alcohol abuse adversely affects essentially all the organs of the body, either directly or indirectly. Ethanol may contribute to brain damage via inflammation. Ethanol may also alter CNS immunocompetence and further the progression of certain CNS infections. Nuclear factor (NF)-kappa B helps regulate inflammatory gene expression in glia. It is possible that ethanol effects on CNS pathology are partly a consequence of ethanol modulation of NF-kappa B-associated pathways in glia. We have assessed the effects of 0.5-6 h ethanol exposure on cytokine (5 ng/ml interleukin-1 beta + 100 ng/ml interferon gamma + 30 ng/ml tumor necrosis factor-alpha)-induced NF-kappa B activation in human A172 astroglial cells. Immunoblot analysis indicated that NF-kappa B p65 nuclear translocation occurred within 0.5 h after cytokine stimulation. Stimulation in the presence of ethanol resulted in increased nuclear p65 levels at 3 h, with 200 mM causing a greater increase than 50 mM ethanol. Gel shift assay data suggested that cytokine-induced NF-kappa B binding activity was greatest in cells exposed to 50 mM ethanol, followed by 200 and 0 mM ethanol exposed cells, respectively. Thus, in cytokine-stimulated cells, 200 mM ethanol resulted in greater nuclear p65 levels, yet, 50 mM ethanol exposure resulted in more pronounced DNA binding by NF-kappa B. These findings demonstrate that acute ethanol enhances p65 activity in human astroglia and further support the hypothesis that ethanol-mediated brain pathology involves modulation of NF-kappa B pathways. A better understanding of the mechanistic events involved in ethanol-induced CNS pathology should provide for therapeutic strategies to combat detrimental effects of alcohol on the CNS.
Davis
Randall L
RL
Alcohol and Brain Research Laboratory, Department of Pharmacology and Neuroscience, Lubbock, TX 79430, USA. randall.davis@ttuhsc.edu
Syapin
Peter J
PJ
D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*
D016207:Cytokines; D016328:NF-kappa B; D000431:Ethanol