Interleukin-6 and the interleukin-6 receptor in the human adrenal gland: Expression and effects on steroidogenesis
Interleukin-6 and the interleukin-6 receptor in the human adrenal gland: Expression and effects on steroidogenesis
复制标题
DOI：
10.1210/jc.82.7.2343
复制
发表时间：
1997-07-01
影响因子：
5.8
通讯作者：
Scherbaum, WA
中科院分区：
文献类型：
--
作者：
Path, G;Bornstein, SR;Scherbaum, WA
白细胞介素（IL）-6是人下丘脑-垂体-肾上腺轴的有效激活剂。在人类中长期施用IL-6后，皮质醇显著升高，而ACTH水平减弱。因此，我们研究了IL-6和/或IL-6受体（IL-6 R）是否在人肾上腺中表达，以及IL-6是否可以通过直接作用于原代培养的肾上腺细胞而引起类固醇激素的释放。用RT-PCR和免疫组化方法检测IL-6和IL-6 R的表达，并观察IL-6对体外人肾上腺类固醇生成的影响。为了避免巨噬细胞介导的效应，我们使用特异性小鼠抗人CD 68和羊抗小鼠IgG结合磁珠从巨噬细胞中去除肾上腺原代培养物。结果表明：1）IL-6和IL-6 R在肾上腺细胞培养物中表达，包括所有细胞类型和去除巨噬细胞的细胞类型，2）IL-6 R主要表达于网状细胞和内束状细胞，肾小球和髓质的阳性信号出现在单个细胞中;和3）IL-6在体外调节盐皮质激素、糖皮质激素和雄激素的肾上腺合成，依赖于时间和剂量，不存在巨噬细胞。24小时后，醛固酮分泌增加到基础分泌的172 +/-28%SEM，皮质醇增加到177 +/-27%SEM，脱氢表雄酮增加到153 +/-20%SEM。这些发现，结合以前的研究，表明IL-6通过下丘脑和垂体发挥其急性作用。然而，在肾上腺中，IL-6似乎是应激反应的长期调节剂，整合了所有皮质区对免疫和内分泌系统刺激的反应。
Interleukin (IL)-6 is a potent activator of the human hypothalamicpituitary-adrenal axis. After chronic administration of IL-6 in humans, there is a substantial elevation of cortisol, whereas ACTH levels are blunted. Thus, we investigated whether IL-6 and/or the IL-6 receptor (IL-6R) are expressed in the human adrenal gland and whether IL-6 could cause the release of steroid hormones by a direct action on adrenal cells in primary culture. The expression of IL-6 and IL-6R was investigated with RT-PCR and immunohistochemistry, and the effects on human adrenal steroidogenesis were tested with IL-6 in vitro. To avoid effects mediated by macrophages, we depleted adrenal primary cultures from macrophages using specific mouse antihuman CD68 and sheep antimouse IgG conjugated magnetic beads. The results showed that: 1) IL-6 and IL-6R are expressed in adrenal cell cultures, including all cell types and those depleted of macrophages; 2) IL-6R is mainly expressed in the zona reticularis and the inner zona fasciculata; positive signals from the zona glomerulosa and the medulla occurred in single cells; and 3) IL-6 regulates adrenal synthesis of mineralocorticoids, glucocorticoids, and androgens in vitro, dependent on time and dose, in the absence of macrophages. After 24 h, aldosterone secretion increased to 172 +/- 28% SEM, cortisol to 177 +/- 27% SEM, and dehydroepiandrosterone to 153 +/- 20% SEM of basal secretion. These findings, in combination with previous investigations, suggest that IL-6 exerts its acute action via the hypothalamus and the pituitary. In the adrenal gland, however, IL-6 seems to be a long-term regulator of stress response, integrating the responses of all cortical zones to stimuli from the immune and endocrine system.