Ethanol inhibits prolactin- and tumor necrosis factor-alpha-, but not gamma interferon-induced expression of intercellular adhesion molecule-1 in human astrocytoma cells

In humans, alcohol consumption has multiple effects on the immune system. D espite an increase in our understanding of the effects of alcohol on the im mune system, little is known about the effect of alcohol on the neuroimmune response. In the central nervous system (CNS), astrocytes and microglial f unction as immune effector cells. In response to infection of injury, astro cytes increase in number and size, express several proinflammatory cytokine s, MHC class I and II antigens, and several adhesion molecules, including i ntercellular adhesion molecule-1 (ICAM-1). Interactions between ICAM-1 and its counter-receptors play an important role in the regulation of neuroimmu ne response. In this study, cultured human astrocytoma cells were used to e xamine the effect of ethanol on ICAM-1 expression. Western blot analyses sh ow that quiescent astrocytes express, at least, four immunoreactive ICAM-1 proteins with apparent molecular weights 55, 67, 82, and 90 kDa. Incubation of human astrocytoma cells with tumor necrosis factor-alpha (TNF-alpha) or prolactin (PRL) resulted in marked increases in all four immunoreactive IC AM-1 proteins. In the presence of ethanol, however, PRL- and TNF-alpha-indu ced increases in all four immunoreactive ICAM-1 proteins were markedly inhi bited. ICAM-1 is a cell surface transmembrane glycoprotein. Using a cell su rface specific ICAM-1 adhesion assay we found that in human astrocytoma cel ls TNF-alpha, interferon gamma (IFN-gamma) and PRL increased cell surface I CAM-1 expression. Consistent with our Western blot analyses, ethanol signif icantly inhibited TNF-alpha- and PRL-induced cell surface ICAM-1 expression . By contrast, IFN-gamma-induced ICAM-1 expression was not inhibited by exp osure of the cells to ethanol. Expression of ICAM-1 is regulated predominan tly at the transcriptional level. In the present report, we show that TNF-a lpha increased ICAM-1 mRNA levels in human astrocytoma cells and that ethan ol markedly blocked TNF-alpha-induced increases in ICAM-1 mRNA levels. Furt her, we found that PRL-induced ICAM-1 expression was, at least in part, due to a PRL-induced increase in TNF-alpha syntheses and secretion. Our result s clearly indicate that ethanol has a pronounced effect on ICAM-1 expressio n in human astrocytoma cells, thus suggesting that ETOH exposure may impair the immune response in the CNS by blocking leukocytes adhesion and migrati on into the CNS in response to injury or infection. J. Cell. Biochem. 77:45 5-464, 2000. (C) 2000 Wiley-Liss. Inc.