ACUTE-PHASE RESPONSE OF HUMAN HEPATOCYTES - REGULATION OF ACUTE-PHASE PROTEIN-SYNTHESIS BY INTERLEUKIN-6
ACUTE-PHASE RESPONSE OF HUMAN HEPATOCYTES - REGULATION OF ACUTE-PHASE PROTEIN-SYNTHESIS BY INTERLEUKIN-6
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DOI：
10.1002/hep.1840120517
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发表时间：
1990-11-01
期刊：
影响因子：
13.5
通讯作者：
HEINRICH, PC
中科院分区：
文献类型：
--
作者：
CASTELL, JV;GOMEZLECHON, MJ;HEINRICH, PC
原代培养中的人肝细胞被用作模型系统，以研究在人肝脏中诱导急性期反应所涉及的机制。将肝细胞与逐渐增加量的重组人白细胞介素-1.β.、重组人白细胞介素-6和肿瘤坏死因子-α一起温育。在mRNA和蛋白质水平上研究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-蛋白质合成。而且，通过用特异性抗血清进行免疫沉淀测量的纤维蛋白原和α1-抗胰蛋白酶合成以剂量依赖性、时间依赖性方式增加，而白蛋白合成减少至对照的约50％。孵育 20 小时后，在 100 至 300 单位重组白细胞介素 6/ml 培养基中观察到最大效果。尽管合成的糖皮质激素地塞米松稍微调节了重组白细胞介素6的作用，但这并不是诱导人肝细胞中急性期蛋白合成的绝对要求。脉冲追踪实验表明，急性期蛋白从细胞中消失的时间过程及其在培养基中的出现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在翻译前水平发挥其对急性期蛋白合成的调节作用。
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.