Microarray analysis reveals interleukin-6 as a novel secretory product of the hypothalamo-neurohypophyseal system

Microarray analysis reveals interleukin-6 as a novel secretory product of the hypothalamo-neurohypophyseal system
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DOI:
10.1074/jbc.m209902200
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发表时间:
2003-05-23
影响因子:
4.8
通讯作者:
Murphy, D
Murphy, D
中科院分区:
生物学2区
文献类型:
--
作者:
Ghorbel, MT;Sharman, G;Murphy, D

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脱水导致下丘脑-神经垂体系统(HNS)的生理激活是垂体后叶大量释放加压素(VP)。这伴随着HNS的功能重塑。在这项研究中,我们使用cDNA阵列,试图确定基因表现出差异表达的下丘脑脱水后。我们的研究揭示了9个候选基因,其中包括白细胞介素-6(IL-6)作为一个假定的新的分泌产物的HNS值得进一步分析。原位杂交和免疫细胞化学证实IL-6在下丘脑视上核和室旁核表达。通过免疫荧光双染色,我们发现IL-6与VP在SON和PVN中很大程度上共定位。原位杂交、免疫细胞化学和Western印迹均显示IL-6在脱水后SON和PVN中上调,从而验证了阵列数据。同样的脱水刺激导致IL-6免疫反应性的增加,在正中隆起的内部区域的轴突和IL-6样物质在垂体后叶的显着减少。因此,我们认为,IL-6采取相同的分泌途径VP和分泌垂体后叶后的生理刺激。
Physiological activation of the hypothalamo-neurohypophyseal system (HNS) by dehydration results is a massive release of vasopressin (VP) from the posterior pituitary. This is accompanied by a functional remodeling of the HNS. In this study we used cDNA arrays in an attempt to identify genes that exhibit differential expression in the hypothalamus following dehydration. Our study revealed nine candidate genes, including interleukin-6 (IL-6) as a putative novel secretory product of HNS worthy of further analysis. In situ hybridization and immunocytochemistry confirmed that IL-6 is robustly expressed in the supraoptic (SON) and the paraventricular (PVN) nuclei of the hypothalamus. By double-staining immunofluorescence we showed that IL-6 is largely co-localized with VP in the SON and PVN. In situ hybridization, immunocytochemistry, and Western blotting all revealed IL-6 up-regulation in the SON and PVN following dehydration, thus validating the array data. The same dehydration stimulus resulted in an increase in IL-6 immunoreactivity in the axons of the internal zone of the median eminence and a marked reduction in IL-6-like material in the posterior pituitary gland. We thus suggest that IL-6 takes the same secretory pathway as VP and is secreted from the posterior pituitary following a physiological stimulus.