Effects of cytokine combinations on acute phase protein production in two human hepatoma cell lines.
Effects of cytokine combinations on acute phase protein production in two human hepatoma cell lines.
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DOI：
10.4049/jimmunol.146.9.3032
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发表时间：
1991-05
影响因子：
4.4
通讯作者：
A. Mackiewicz;T. Speroff;M. Ganapathi;I. Kushner
中科院分区：
文献类型：
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作者：
A. Mackiewicz;T. Speroff;M. Ganapathi;I. Kushner
我们评估了四种细胞因子的二元组合对两种人肝癌细胞系中阳性急性期蛋白α-1抗胰凝乳蛋白酶、触珠蛋白和纤维蛋白原以及阴性急性期蛋白白蛋白和甲胎蛋白（AFP）产生的影响。细胞因子组合对五种蛋白质的影响各不相同;每种蛋白质对细胞因子组合的反应均表现出独特和特异的模式。在Hep G2细胞中，抗胰凝乳蛋白酶由所有四种细胞因子IL-6、IL-1、TNF-α和转化生长因子β 1单独诱导，它们在二元组合中的作用可归因于相加或最小协同相互作用。纤维蛋白原仅由IL-6诱导，并且该诱导被IL-1 α、TNF-α或转化生长因子β 1抑制。结合珠蛋白也仅由IL-6诱导，但TNF-α是在所有浓度的IL-6下抑制这种诱导的唯一细胞因子。四种细胞因子单独下调AFP和白蛋白的产生。然而，四种细胞因子的二元组合在大多数情况下是简单相加的，在抑制AFP产生方面，而细胞因子的组合对白蛋白产生的抑制作用与简单相加作用显著不同。这些观察结果与细胞因子组合对其他急性期蛋白的影响的研究一起表明，各种急性期蛋白对细胞因子的不同组合的反应不同，并且存在通过细胞因子相互作用高度特异性调节个体血浆蛋白合成的潜力。这些发现意味着体内急性期反应代表了基因表达中多个单独调节的变化的综合总和。
We evaluated the effects of binary combinations of four cytokines on production of the positive acute phase proteins alpha-1 antichymotrypsin, haptoglobin and fibrinogen, and the negative acute phase proteins albumin and alpha-fetoprotein (AFP) in two human hepatoma cell lines. The effects of the cytokine combinations on the five proteins varied; each protein exhibited a unique and specific pattern of response to the cytokine combinations. In Hep G2 cells, antichymotrypsin was induced by all four cytokines, IL-6, IL-1, TNF-alpha, and transforming growth factor beta 1 alone, and their effects in binary combinations could be attributed to additive or minimally synergistic interactions. Fibrinogen was induced only by IL-6 and this induction was inhibited by IL-1 alpha, TNF-alpha or transforming growth factor beta 1. Haptoglobin was also induced only by IL-6, but TNF-alpha was the only cytokine that inhibited this induction at all concentrations of IL-6. Each of the four cytokines alone down regulated production of AFP and albumin. However, binary combinations of the four cytokines were simply additive, for the most part, in inhibiting AFP production, whereas the inhibitory effects of combinations of cytokines on albumin production differed significantly from simple additive effects. These observations, taken together with studies of effects of cytokine combinations on other acute phase proteins, indicate that the various acute phase proteins respond differently to different combinations of cytokines and that the potential exists for highly specific regulation of synthesis of individual plasma proteins by cytokine interactions. These findings imply that the acute phase response in vivo represents the integrated sum of multiple, separately regulated changes in gene expression.