CYTOKINES DECREASE APOLIPOPROTEIN ACCUMULATION IN MEDIUM FROM HEP G2 CELLS
CYTOKINES DECREASE APOLIPOPROTEIN ACCUMULATION IN MEDIUM FROM HEP G2 CELLS
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DOI：
10.1161/01.atv.14.1.8
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发表时间：
1994-01-01
期刊：
影响因子：
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通讯作者：
VERDERY, PB
中科院分区：
文献类型：
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作者：
ETTINGER, WH;VARMA, VK;VERDERY, PB
细胞因子是炎症的重要生化介质，可导致体内血浆胆固醇浓度迅速下降。细胞因子可能导致获得性低胆固醇血症的一种机制是减少肝脏载脂蛋白的合成和分泌。为了验证这一假设，我们将Hep G2细胞与人重组肿瘤坏死因子-α、白细胞介素-1 β和白细胞介素-6孵育。孵育24小时后，每种细胞因子均导致培养基中载脂蛋白（ape）A-I、apoB和卵磷脂：胆固醇酰基转移酶（LCAT）活性浓度呈剂量相关性降低。细胞因子对载脂蛋白蓄积的影响不受脂肪酸预孵育Hep G2细胞的影响。细胞因子以剂量相关的方式降低细胞apoA-I mRNA的浓度，但不影响细胞apoB mRNA的浓度。在细胞因子孵育的细胞培养基中，甘油三酯和胆固醇的浓度也降低。通过[C-14]乙酸酯掺入计算总细胞甾醇合成速率。与白细胞介素-6孵育的细胞甾醇合成率增加31%，但甾醇分泌减少41%。这些数据表明，这些细胞因子可以减少肝脏合成和/或载脂蛋白的分泌，这可能部分解释了急性和慢性炎症期间观察到的获得性低胆固醇血症。
Cytokines, important biochemical mediators of inflammation, cause a rapid fall in the plasma concentration of cholesterol in vivo. One mechanism by which cytokines may cause acquired hypocholesterolemia is by decreasing the hepatic synthesis and secretion of apolipoproteins. To test this hypothesis, we incubated Hep G2 cells with human recombinant tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6. Each of the cytokines resulted in a dose-related reduction in the concentrations of apolipoprotein (ape) A-I, apoB, and lecithin: cholesterol acyltransferase (LCAT) activity in the medium after 24 hours of incubation. The effect of cytokines on apolipoprotein accumulation was not affected by preincubation of Hep G2 cells with fatty acids. Cytokines decreased the concentration of cellular apoA-I mRNA in a dose-related fashion but did not affect cellular concentrations of apoB mRNA. The concentrations of triglyceride and cholesterol were also reduced in the medium of cells incubated with cytokines. Total cell sterol synthesis rates were calculated by [C-14]acetate incorporation. Cells incubated with interleukin-6 had a 31% increase in sterol synthesis rate but a 41% decrease in sterol secretion. These data suggest that these cytokines can decrease the hepatic synthesis and/or secretion of apolipoproteins and that this may explain, in part, the acquired hypocholesterolemia seen during acute and chronic inflammation.