Castell J V, Gómez-Lechón M J, David M, Fabra R, Trullenque R, Heinrich P C
Institut für Biochemie, RWTH Aachen, Federal Republic of Germany.
Hepatology. 1990 Nov;12(5):1179-86. doi: 10.1002/hep.1840120517.
Human hepatocytes in primary culture were used as a model system to investigate the mechanism(s) involved in the induction of the acute-phase response in human liver. Hepatocytes were incubated with increasing amounts of recombinant human interleukin-1 beta, recombinant interleukin-6 and tumor necrosis factor-alpha. Synthesis of C-reactive protein was studied at the mRNA and protein levels. Only recombinant interleukin-6 was capable of inducing C-reactive protein-mRNA and C-reactive protein-protein synthesis. Also, fibrinogen and alpha-1-antitrypsin synthesis measured by immunoprecipitation with specific antisera increased in a dose-dependent, time-dependent manner, whereas albumin synthesis decreased to about 50% of controls. Maximal effects were observed at 100 to 300 units of recombinant interleukin-6/ml culture medium after 20 hr of incubation. Although the synthetic glucocorticoid dexamethasone slightly modulated the effect of recombinant interleukin-6, it was not an absolute requirement for the induction of acute-phase protein synthesis in human hepatocytes. In pulse-chase experiments it was shown that the time course of the disappearance of the acute-phase proteins from the cells and their appearance in the medium is not influenced by recombinant interleukin-6. This finding suggests that recombinant interleukin-6 exerts its regulatory effect on acute-phase protein synthesis at the pretranslational level.
原代培养的人肝细胞被用作模型系统，以研究人肝脏中参与急性期反应诱导的机制。将肝细胞与越来越多的重组人白细胞介素-1β、重组白细胞介素-6和肿瘤坏死因子-α一起孵育。在mRNA和蛋白质水平上研究了C反应蛋白的合成。只有重组白细胞介素-6能够诱导C反应蛋白mRNA和C反应蛋白的合成。此外，用特异性抗血清免疫沉淀法测定的纤维蛋白原和α-1-抗胰蛋白酶的合成以剂量依赖性和时间依赖性方式增加，而白蛋白合成降至对照的约50%。孵育20小时后，在100至300单位重组白细胞介素-6/毫升培养基中观察到最大效应。尽管合成糖皮质激素地塞米松对重组白细胞介素-6的作用有轻微调节，但它不是人肝细胞中诱导急性期蛋白合成的绝对必要条件。在脉冲追踪实验中表明，急性期蛋白从细胞中消失及其在培养基中出现的时间进程不受重组白细胞介素-6的影响。这一发现表明重组白细胞介素-6在翻译前水平对急性期蛋白合成发挥调节作用。
