DeVito W J, Stone S, Mori K
Division of Endocrinology, University of Massachusetts Medical Center, Worcester 01655, USA.
Endocrinology. 1997 Mar;138(3):922-8. doi: 10.1210/endo.138.3.4964.
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.
虽然长期饮酒的免疫抑制作用已有充分记录，但乙醇对神经免疫反应的影响却知之甚少。我们之前证明，催乳素是一种有效的促细胞分裂剂，可诱导培养的大鼠星形胶质细胞中几种炎性细胞因子的表达，包括肿瘤坏死因子-α（TNFα）。本研究的目的是检测乙醇对培养的大鼠星形胶质细胞中催乳素诱导的细胞增殖及TNFα表达的影响。我们发现，低浓度乙醇可阻断催乳素诱导的[3H]胸腺嘧啶核苷掺入增加及TNFα水平升高。相比之下，乙醇对血小板衍生生长因子或成纤维细胞生长因子诱导的[3H]胸腺嘧啶核苷掺入增加没有影响。放射性配体结合分析显示，乙醇不影响催乳素受体结合。我们还检测了产前酒精暴露（PAE）对催乳素诱导的细胞增殖及细胞因子表达的影响。妊娠最后5天的PAE使在培养基中无乙醇条件下生长的细胞中催乳素诱导的[3H]胸腺嘧啶核苷掺入增加及TNFα水平升高减弱。向原代PAE星形胶质细胞培养物中添加乙醇导致基础[3H]胸腺嘧啶核苷掺入适度增加，但完全阻断了催乳素诱导的[3H]胸腺嘧啶核苷掺入增加及TNFα水平升高。相比之下，血小板衍生生长因子和血清（10%）诱导的[3H]胸腺嘧啶核苷掺入增加保持不变。总之，这些数据表明乙醇可阻断培养的大鼠星形胶质细胞中催乳素诱导的细胞增殖及TNFα表达，这与乙醇在体内可能抑制星形胶质细胞反应一致。
