Tuma D J, Todero S L, Barak-Bernhagen M, Sorrell M F
Veterans Affairs Alcohol Research Center, Department of Veterans Affairs Medical Center, Omaha, NE 68105, USA.
Alcohol Clin Exp Res. 1996 May;20(3):579-83. doi: 10.1111/j.1530-0277.1996.tb01096.x.
The effects of chronic ethanol administration on the endocytosis of three representative cytokines were investigated in isolated rat hepatocytes. When hepatocytes were isolated from rats that were fed an ethanol liquid diet for 12 to 13 weeks, these cells exhibited a decreased ability to internalize and degrade transforming growth factor-alpha, tumor necrosis factor-alpha and interleukin-6, compared with hepatocytes from the pair-fed controls. This impaired endocytosis of all three cytokines was accompanied by significant decreases in the amount of hepatocyte surface-bound cytokine. Changes in cytokine binding to surface receptors and reduced rates of receptor-cytokine complex internalization into the cells seem to be major contributors to defective endocytosis in hepatocytes from the ethanol-fed rats. Impaired hepatocyte endocytosis could lead to altered steady-state levels of cytokines in the liver and modified physiological responses to cytokines. These changes could affect homeostasis among the various cell types in the liver and could contribute to liver dysfunction and injury.
在分离的大鼠肝细胞中研究了长期给予乙醇对三种代表性细胞因子内吞作用的影响。当从喂食乙醇液体饲料12至13周的大鼠中分离肝细胞时，与配对喂食对照的肝细胞相比，这些细胞内化和降解转化生长因子-α、肿瘤坏死因子-α和白细胞介素-6的能力降低。所有三种细胞因子的内吞作用受损伴随着肝细胞表面结合细胞因子数量的显著减少。细胞因子与表面受体结合的变化以及受体-细胞因子复合物内化进入细胞的速率降低似乎是乙醇喂养大鼠肝细胞内吞作用缺陷的主要原因。肝细胞内吞作用受损可能导致肝脏中细胞因子的稳态水平改变以及对细胞因子的生理反应改变。这些变化可能影响肝脏中各种细胞类型之间的稳态，并可能导致肝功能障碍和损伤。
