Transcriptional regulation of oxytocin receptor by interleukin-1β and interleukin-6
Transcriptional regulation of oxytocin receptor by interleukin-1β and interleukin-6
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DOI：
10.1210/en.142.4.1380
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发表时间：
2001-04-01
期刊：
影响因子：
4.8
通讯作者：
Mitchell, BF
中科院分区：
文献类型：
--
作者：
Schmid, B;Wong, S;Mitchell, BF
妊娠后期催产素受体的上调主要是由于信使RNA合成的增加。人类OT受体基因的5'侧区含有核因子-白细胞介素-6 （NF-IL6）的几个假定的结合位点，也称为CAAT/增强子结合蛋白- β。这种伊朗作用因子调节参与急性炎症反应的基因表达。促炎细胞因子，如IL-1 β或IL-6，被认为是早产和足月分娩的介质，特别是与宫内感染有关。我们假设IL-1 β和IL-6在人子宫内膜细胞中诱导OT受体基因表达，而这是由NF-IL6和OT受体基因5'侧区的同源反应元件介导的。与假设相反，通过核糖核酸酶保护分析，IL-1 β和IL-6处理均导致OT受体信使RNA显著降低。使用电泳迁移率转移测定，我们已经证明NF-IL6存在于低水平，似乎在用IL-1 β或IL-6治疗后增加。通过对HeLa细胞的缺失分析和功能转染研究，我们证明了OT受体基因启动子具有基本活性，并受到IL-1 β和IL-6的负调控。IL-1 β和IL-6的这种抑制能力取决于OT受体启动子的- 1203/- 722区域，该区域包含NF-IL6、急性期反应元件和NF-kappaB的结合位点。我们的研究结果表明，IL-1 β和IL-6在人类OT受体基因的转录调节中起作用。
The up-regulation of oxytocin (OT) receptors in late pregnancy results principally from increased synthesis of messenger RNA. The 5'-flanking region of the human OT receptor gene contains several putative binding sites for nuclear factor-interleukin-6 (NF-IL6), also known as CAAT/enhancer binding protein-beta. This Irans-acting factor modulates the expression of genes involved in acute inflammatory responses. Proinflammatory cytokines, such as IL-1 beta or IL-6, have been implicated as mediators in both preterm and term labor, par ticularly in association with intrauterine infection. We hypothesized that IL-1 beta and IL-6 induce OT receptor gene expression in human myometrial cells, and this is mediated by NF-IL6 and cognate response elements in the 5'-flanking region of the OT receptor gene. Contrary to the hypothesis, both IL-1 beta and IL-6 treatment resulted in a significant decrease in OT receptor messenger RNA measured by ribonuclease protection analysis. Using electrophoretic mobility shift assay, we have shown that NF-IL6 is present at low levels that appear to be increased after treatment with either IL-1 beta or IL-6. Using deletion analysis and functional transfection studies in HeLa cells, we demonstrated that the OT receptor gene promoter displays constitutive basal activity and is negatively regulated by both IL-1 beta and IL-6. This suppressive ability of IL-1 beta and IL-6 depends on the - 1203/- 722 region of the OT receptor promoter, which contains binding sites for NF-IL6, acute phase response element, and NF-kappaB. Our findings suggest a role for IL-1 beta and IL-6 in the transcriptional regulation of the human OT receptor gene.