title: Low concentrations of ethanol inhibits prolactin-induced mitogenesis and cytokine expression in cultured astrocytes.
abstract: Whereas the immunosuppressive effects of chronic alcohol use have been well documented, little is known about the effect of ethanol on the neuroimmune response. We previously demonstrated that PRL is a potent mitogen and induces the expression of several inflammatory cytokines, including tumor necrosis factor-alpha (TNF alpha) in cultured rat astrocytes. The aim of this study was to examine the effects of ethanol on PRL-induced mitogenesis and TNF alpha expression in cultured rat astrocytes. We found that low concentrations of ethanol blocked PRL-induced increases in [3H]thymidine incorporation and TNF alpha levels. In contrast, ethanol had no effect on platelet-derived growth factor- or fibroblast growth factor-induced increases in [3H]thymidine incorporation. Radioligand binding analysis revealed that ethanol did not effect PRL receptor binding. We also examined the effect of prenatal alcohol exposure (PAE) on PRL-induced mitogenesis and cytokine expression. PAE during the last 5 days of gestation blunted the PRL-induced increase in [3H]thymidine incorporation and TNF alpha levels in cells grown in the absence of ethanol in the culture medium. Addition of ethanol to primary PAE astrocyte cultures resulted in a modest increase in basal [3H]thymidine incorporation, but completely blocked the PRL-induced increase in [3H]thymidine incorporation and TNF alpha levels. In contrast, platelet-derived growth factor- and serum (10%)-induced increases in [3H]thymidine incorporation remained intact. Together, these data indicate that ethanol blocks PRL-induced mitogenesis and the expression of TNF alpha in cultured rat astrocytes and are consistent with the possible inhibition of the astrocytic response by ethanol in vivo.
authors.affiliation: Division of Endocrinology, University of Massachusetts Medical Center, Worcester 01655, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: DeVito
authors.forename: S
authors.initials: S
authors.lastname: Stone
authors.forename: K
authors.initials: K
authors.lastname: Mori
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008938:Mitosis / Q000187:drug effects*; D009994:Osmolar Concentration; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011388:Prolactin / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D011388:Prolactin; D013936:Thymidine