ACTION OF RECOMBINANT HUMAN INTERLEUKIN-6, INTERLEUKIN-1-BETA AND TUMOR NECROSIS FACTOR-ALPHA ON THE MESSENGER-RNA INDUCTION OF ACUTE-PHASE PROTEINS
ACTION OF RECOMBINANT HUMAN INTERLEUKIN-6, INTERLEUKIN-1-BETA AND TUMOR NECROSIS FACTOR-ALPHA ON THE MESSENGER-RNA INDUCTION OF ACUTE-PHASE PROTEINS
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DOI：
10.1002/eji.1830180513
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发表时间：
1988-05-01
影响因子：
5.4
通讯作者：
HEINRICH, PC
中科院分区：
文献类型：
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作者：
ANDUS, T;GEIGER, T;HEINRICH, PC
以大鼠肝癌细胞系Fao为材料，研究了三种炎症介质对几种急性时相蛋白mRNA表达的调节作用。在10-6 M地塞米松β-加入重组人IL 6（rhIL 6）后纤维蛋白原mRNA水平增加6倍。rhIL1.beta.或重组人肿瘤坏死因子α。（rhTNF α）对β基本上没有影响-纤维蛋白原mRNA诱导，但在地塞米松存在下导致α 1-酸性糖蛋白mRNA增加20倍。另一方面，rhIL 6是α 1-酸性糖蛋白mRNA合成的弱得多的刺激剂。所有三种介质都将白蛋白mRNA浓度降低至对照组的约30%。而β-的诱导纤维蛋白原mRNA被地塞米松增强，合成的糖皮质激素类似物是刺激α 1-酸性糖蛋白mRNA的绝对需要。阴性急性时相蛋白白蛋白的mRNA水平仅由地塞米松诱导5倍。β-加入rhIL 6后，纤维蛋白原mRNA的诱导立即开始，并在12 - 18 h之间达到最大值。相比之下，α 1-酸性糖蛋白mRNA合成的时间过程显示出8小时的滞后期，随后在rhIL 1 β后增加至20小时。rhTNF.alpha.导致α 1-酸性糖蛋白mRNA的增加更加延迟。而在β. -的情况下纤维蛋白原mRNA诱导在三种介质的不同浓度之间没有观察到协同效应，rhIL 6/rhIL 1 β的组合。以及rhIL 6/rhTNF α。或rhIL 1 β/ rhTNF.alpha.协同调节α 1-酸性糖蛋白和白蛋白mRNA。它的结论是，离散的急性期蛋白质的调节不同的炎症介质IL 6，IL 1 β。和TNF α，表明急性期响应比先前假设的更复杂。本研究中使用的Fao细胞系证明是急性期蛋白调节的理想模型，适合于区分炎症介质IL 6和IL 1/TNF α。
The rat hepatoma cell line Fao was used to study the role of three inflammatory mediators on the mRNA regulation of several acute-phase proteins. In the presence of 10-6 M dexamethasone .beta.-fibrinogen mRNA levels increased 6-fold after addition of recombinant human IL 6 (rhIL6). rhIL1.beta. or recombinant human tumor necrosis factor .alpha. (rhTNF.alpha.) had essentially no effect on .beta.-fibrinogen mRNA induction but led to a 20-fold increase in .alpha.1-acid glycoprotein mRNA in the presence of dexamethasone. On the other hand, rhIL6 was a much weaker stimulator of .alpha.1-acid glycoprotein mRNA synthesis. All three mediators reduced albumin mRNA concentrations to about 30% of controls. Whereas the induction of .beta.-fibrinogen mRNA was potentiated by dexamethasone, the synthetic glucocorticoid analog was an absolute requirement for the stimulation of .alpha.1-acid glycoprotein mRNA. The mRNA levels of the negative acute-phase protein albumin were induced 5-fold by dexamethasone alone. The .beta.-fibrinogen mRNA induction started immediately after addition of rhIL6 and reached a maximum between 12 and 18 h. In contrast, the time-course for .alpha.1-acid glycoprotein mRNA synthesis showed a lag phase of 8 h followed by an increase up to 20 h after rhIL1.beta.. rhTNF.alpha. led to an even more delayed increase in .alpha.1-acid glycoprotein mRNA. Whereas in the case of .beta.-fibrinogen mRNA induction no synergistic effect was observed between various concentrations of the three mediators, the combination of rhIL 6/rhIL1.beta. as well as rhIL6/rhTNF.alpha. or rhIL1.beta./rhTNF.alpha. regulated synergistically .alpha.1-acid glycoprotein and albumin mRNA. It is concluded that discrete acute-phase proteins are regulated differently by the inflammatory mediators IL 6, IL 1.beta. and TNF.alpha., indicating that the acute-phase response is more complex than previously assumed. The Fao cell line used in this study turned out to be an ideal model for acute-phase protein regulation, suitable for the discrimination between the inflammatory mediators IL6 and IL1/TNF.alpha.