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. Despite an increase in our understanding of the effects of alcohol on the immune system, little is known about the effect of alcohol on the neuroimmune response. In the central nervous system (CNS), astrocytes and microglial function as immune effector cells. In response to infection of injury, astrocytes increase in number and size, express several proinflammatory cytokines, MHC class I and II antigens, and several adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1). Interactions between ICAM-1 and its counter-receptors play an important role in the regulation of neuroimmune response. In this study, cultured human astrocytoma cells were used to examine the effect of ethanol on ICAM-1 expression. Western blot analyses show 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 ICAM-1 proteins. In the presence of ethanol, however, PRL- and TNF-alpha-induced increases in all four immunoreactive ICAM-1 proteins were markedly inhibited. ICAM-1 is a cell surface transmembrane glycoprotein. Using a cell surface specific ICAM-1 adhesion assay we found that in human astrocytoma cells TNF-alpha, interferongamma (IFN-gamma) and PRL increased cell surface ICAM-1 expression. Consistent with our Western blot analyses, ethanol significantly inhibited TNF-alpha- and PRL-induced cell surface ICAM-1 expression. By contrast, IFN-gamma-induced ICAM-1 expression was not inhibited by exposure of the cells to ethanol. Expression of ICAM-1 is regulated predominantly at the transcriptional level. In the present report, we show that TNF-alpha increased ICAM-1 mRNA levels in human astrocytoma cells and that ethanol markedly blocked TNF-alpha-induced increases in ICAM-1 mRNA levels. Further, 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 results clearly indicate that ethanol has a pronounced effect on ICAM-1 expression in human astrocytoma cells, thus suggesting that ETOH exposure may impair the immune response in the CNS by blocking leukocytes adhesion and migration into the CNS in response to injury or infection.