Corticosteroid-binding globulin synthesis regulation by cytokines and glucocorticoids in human hepatoblastoma-derived (HepG2) cells
Corticosteroid-binding globulin synthesis regulation by cytokines and glucocorticoids in human hepatoblastoma-derived (HepG2) cells
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DOI：
10.1210/jc.82.11.3758
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发表时间：
1997-11-01
影响因子：
5.8
通讯作者：
Pugeat, M
中科院分区：
文献类型：
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作者：
EmptozBonneton, A;Crave, JC;Pugeat, M
脓毒性休克或烧伤患者血浆皮质类固醇结合球蛋白（CBG）浓度显著降低。这种减少表明，急性期反应的介质，如细胞因子和糖皮质激素，可能会影响人体CBG的清除以及肝脏合成。本研究观察了白细胞介素6（IL-6）、IL-1 β和地塞米松对人肝母细胞瘤（HepG 2）细胞株CBG合成的影响，发现在0.1-10 ng/mL的IL-6浓度范围内，HepG 2细胞培养液中CBG的免疫浓度和CBG信使核糖核酸（mRNA）水平呈剂量依赖性降低。CBG免疫浓度的降低百分比在数量上与CBG mRNA水平的降低百分比相似（分别为对照值的29 +/- 6%和39 +/-15%）。相反，正如预期的那样，IL-6剂量依赖性地增加了mRNA水平，（对照值的164 +/- 22%）的α（1）-抗胰蛋白酶，一种阳性急性期蛋白，但不影响性激素结合球蛋白，另一种肝脏蛋白的免疫浓度。单独使用地塞米松并不显著影响CBG分泌或mRNA水平，但剂量依赖性地增加酪氨酸转氨酶mRNA水平，然而，与IL-6联合使用时，地塞米松对IL-6抑制HepG 2细胞中CBG分泌和mRNA具有显著的累加效应，IL-1 β剂量依赖性地刺激CBG分泌（对照值的156 +/-10%），而对CBG mRNA水平没有显著影响。此外，IL-1 β可显著降低IL-6对CBG分泌的抑制作用，但对IL-6对CBG mRNA水平的抑制作用无影响。这些结果表明，IL-1 β作用于HepG 2细胞中CBG的翻译后加工和/或分泌机制。总之，本研究结果有力地支持了以下假设，即感染性休克和烧伤患者血浆CBG浓度的降低与IL-6和糖皮质激素水平的升高有关。
Plasma corticosteroid-binding globulin (CBG) concentrations decrease dramatically in patients with septic shock or burn injury. This decrease suggests that mediators of the acute phase response, such as cytokines and glucocorticoid hormones, might influence clearance as well as liver synthesis of CBG in humans. The present study investigated the effects of interleukin-6 (IL-6), IL-1 beta, and dexamethasone on CBG synthesis by a clone of human hepatoblastoma-derived (HepG2) cell line.In culture medium from HepG2 cells, the immunoconcentration of CBG and the levels of CBG messenger ribonucleic acid (mRNA) were dose dependently decreased in the presence of IL-6 concentrations ranging from 0.1-10 ng/mL. The percent decrease in CBG immunoconcentration was quantitatively similar to the percent decrease in CBG mRNA levels (29 +/- 6% and 39 +/- 15%, respectively, of control values). In contrast, and as expected, IL-6 dose dependently increased the mRNA levels (164 +/- 22% of control values) of alpha(1)-antitrypsin, a positive acute phase protein, but did not affect the immunoconcentration of sex hormone-binding globulin, another liver protein.Dexamethasone alone did not significantly affect CBG secretion or mRNA levels, but did dose-dependently increase tyrosine aminotransferase mRNA levels, which increased to 252 +/- 169 of the control values, However, in combination with IL-6, dexamethasone had a significant additive effect on IL-6 inhibition of CBG secretion and mRNAs in HepG2 cells.IL-1 beta dose-dependently stimulated CBG secretion (156 +/- 10% of control values) with no significant effect on CBG mRNA levels. In addition, IL-1 beta significantly decreased the inhibitory effect of IL-6 on CBG secretion, but had no effect on the inhibitory effect of IL-6 on CBG mRNA levels. These results suggest that IL-1 beta acts on the posttranslation processing and/or secretion mechanisms of CBG in HepG2 cells.Together, the present results strongly support the hypothesis that the decrease in plasma CBG concentrations is associated with the increase in IL-6 and glucocorticoid levels reported in patients with septic shock and burn injury.