ROLE OF INTERLEUKIN-6 IN REGULATING SYNTHESIS OF C-REACTIVE PROTEIN AND SERUM AMYLOID-A IN HUMAN HEPATOMA-CELL LINES
ROLE OF INTERLEUKIN-6 IN REGULATING SYNTHESIS OF C-REACTIVE PROTEIN AND SERUM AMYLOID-A IN HUMAN HEPATOMA-CELL LINES
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DOI：
10.1016/s0006-291x(88)80043-3
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发表时间：
1988-11-30
影响因子：
3.1
通讯作者：
KUSHNER, I
中科院分区：
文献类型：
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作者：
GANAPATHI, MK;MAY, LT;KUSHNER, I
先前的研究已经证明，人肝癌细胞系合成两种主要的人急性期蛋白C-反应蛋白（CRP）和血清淀粉样蛋白A（SAA）不受白细胞介素-1（IL-1）或肿瘤坏死因子α制剂的影响。但在暴露于来自脂多糖激活的单核细胞的条件培养基后增加。我们报告，大肠杆菌衍生的重组人白细胞介素-6（IL-6）的中和抗体能够抑制诱导CRP和SAA的单核细胞条件培养基在NPLC/PRF/5和Hep 3B细胞系。从脂多糖刺激的人成纤维细胞中部分纯化的IL-6和重组衍生的IL-6在NPLC/PRF/5细胞系中以浓度依赖性方式诱导CRP和SAA合成。相反，在Hep 3B细胞中，单独的IL-6对CRP或SAA的诱导没有可辨别的作用，但能够引起α 1-蛋白酶抑制剂和纤维蛋白原的合成增加和白蛋白的合成减少。IL-1和IL-6的加入导致Hep 3B细胞中CRP和SAA的诱导，但在NPLC/PRF/5细胞中没有增加CRP或SAA的反应。这些研究表明，IL-6在两种人肝癌细胞系中诱导CRP和SAA合成中起着核心作用。我们研究的两种肝癌细胞系的不同观察结果可能反映了这些转化细胞系在遗传调控机制或其他细胞内机制方面的差异，细胞外信号通过这些机制影响CRP和SAA基因的表达。此外，我们的发现表明，IL-6调节Hep 3B细胞中CRP和SAA合成的机制不同于参与诱导α 1-蛋白酶抑制剂和纤维蛋白原以及抑制白蛋白合成的机制。
Previous studies have demonstrated that synthesis of the two major human acute phase proteins, C-reactive protein (CRP) and serum amyloid A (SAA), by human hepatoma cell lines was not affected by preparations of interleukin-1 (IL-1) or tumor necrosis factor .alpha. but was increased after exposure to conditioned medium from lipopolysaccharide-activated monocytes. We report that neutralizing antibodies raised against Escherichia coli-derived recombinant human interleukin-6 (IL-6) were capable of inhibiting induction of CRP and SAA by monocyte conditioned medium in both NPLC/PRF/5 and Hep 3B cell lines. Partially purified IL-6 from lipopolysaccharide-stimulated human fibroblasts and recombinant derived IL-6 induced both CRP and SAA synthesis in a concentration dependent manner in the NPLC/PRF/5 cell line. In contrast, in Hep 3B cells, IL-6 alone had no discernable effect on the induction of either CRP or SAA, but was capable of causing increased synthesis of .alpha.1-protease inhibitor and fibrinogen and reduced synthesis of albumin. The addition of IL-1 to IL-6 led to induction of both CRP and SAA in Hep 3B cells, but did not augment the response of either CRP or SAA in NPLC/PRF/5 cells. These studies indicate that IL-6 plays a central role in induction of both CRP and SAA synthesis in the two human hepatoma cell lines. The different observations in the two hepatoma lines we studied likely reflect differences between these transformed cell lines in genetic regulatory mechanisms or other intracellular mechanisms by which extracellular signals affect expression of the CRP and SAA genes. Furthermore, our findings sugest that the mechanisms by which IL-6 regulates synthesis of CRP and SAA in Hep 3B cells differ from those involved in induction of .alpha.1-protease inhibitor and fibrinogen and in inhibition of albumin synthesis.