INTERLEUKIN-6 INHIBITS CORTICOSTEROID-BINDING GLOBULIN SYNTHESIS BY HUMAN HEPATOBLASTOMA-DERIVED (HEP G2) CELLS
INTERLEUKIN-6 INHIBITS CORTICOSTEROID-BINDING GLOBULIN SYNTHESIS BY HUMAN HEPATOBLASTOMA-DERIVED (HEP G2) CELLS
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DOI：
10.1210/en.133.1.291
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发表时间：
1993-07-01
期刊：
影响因子：
4.8
通讯作者：
ROBBINS, J
中科院分区：
文献类型：
--
作者：
BARTALENA, L;HAMMOND, GL;ROBBINS, J
皮质类固醇结合球蛋白（CBG）属于丝氨酸蛋白酶抑制剂超家族，包括α 1-抗胰蛋白酶、α 1-抗胰凝乳蛋白酶和T4结合球蛋白。白细胞介素-6（IL-6），急性期现象的主要介质，增加α 1-抗胰蛋白酶和α 1-抗胰凝乳蛋白酶的合成，并减少T4结合球蛋白的合成由人肝母细胞瘤衍生（Hep G2）细胞。这种效应主要是在转录水平。当Hep G2细胞暴露于不同浓度的IL-6持续不同的时间间隔时，IL-6引起培养基中[S-35]甲硫氨酸标记的CBG免疫沉淀量的剂量和时间依赖性减少。将IL-6与其中和抗体预孵育可以大大降低这种效应，并通过从培养基中去除细胞因子来逆转这种效应。CBG的分泌速率不受细胞暴露于IL-6的影响。CBG mRNA稳态水平降低; mRNA的变化在数量上与分泌蛋白的变化相似。核径流分析未能显示CBG基因转录速率的变化，这些数据表明，IL-6减少CBG合成的Hep G2细胞在转录后水平上发挥作用，可能是通过降低mRNA的稳定性。鉴于IL-6在炎症过程和其他急性期现象中的作用，这些数据表明其对CBG合成的影响可能间接影响皮质醇的生物利用度，并在这些条件下调节稳态过程中发挥作用。
Corticosteroid-binding globulin (CBG) belongs to the superfamily of serine proteinase inhibitors which include alpha1-antitrypsin, alpha1-anti-chymotrypsin, and T4-binding globulin. Interleukin-6 (IL-6), the main mediator of the acute phase phenomenon, increases alpha1-antitrypsin and alpha1-antichymotrypsin synthesis and decreases T4-binding globulin synthesis by human hepatoblastoma-derived (Hep G2) cells. This effect is predominantly at a transcriptional level. When Hep G2 cells were exposed to different concentrations of IL-6 for variable time intervals, IL-6 caused a dose- and time-dependent decrease in the amount of [S-35]methionine-labeled CBG immunoprecipitated in the culture medium. This effect could be greatly reduced by preincubation of IL-6 with its neutralizing antibody and reversed by removing the cytokine from the culture medium. The secretion rate of CBG was not affected by cell exposure to IL-6. CBG mRNA steady state levels were reduced; changes in mRNA were quantitatively similar to changes in secreted protein. Nuclear run-off assays failed to show a change in the rate of transcription of the CBG gene.These data indicate that IL-6 diminishes CBG synthesis by Hep G2 cells acting at a posttranscriptional level, presumably through a reduced stability of mRNA. In view of the role of IL-6 in the inflammatory process and other acute phase phenomena, these data suggest that its effects on CBG synthesis might influence the bioavailability of cortisol indirectly and play a role in regulating the homeostatic process during these conditions.