Interleukin 1 regulates its own receptors in human endometrial cells via distinct mechanisms
Interleukin 1 regulates its own receptors in human endometrial cells via distinct mechanisms
复制标题
DOI：
10.1093/humrep/dep192
复制
发表时间：
2009-09-01
影响因子：
6.1
通讯作者：
Akoum, A.
中科院分区：
文献类型：
--
作者：
Bellehumeur, C.;Blanchet, J.;Akoum, A.
白细胞介素1（IL 1）在人类子宫内膜的生理中起着重要作用，被认为是一种主要的早期胚胎信号。严格控制这种细胞因子的局部子宫内膜作用对正常生殖功能至关重要。子宫内膜细胞中I型和II型IL 1受体（IL 1 R1和IL 1 R2）和IL 1受体拮抗剂（IL 1 RA）的协调调节可能是参与控制IL 1局部效应的主要机制之一。本研究旨在探讨IL 1对人子宫内膜上皮细胞IL 1受体的调节作用。采用免疫荧光染色、酶联免疫吸附试验、蛋白质印迹、核转录（run-on）和实时荧光定量PCR等方法，对KLE子宫内膜上皮细胞系和原代人子宫内膜上皮细胞IL 1 R 1的表达进行研究，细胞似乎通过上调激活IL 1 R1的信号传导的表达而对IL 1起反应，并且通过升高诱饵抑制性IL 1 R2和受体拮抗剂IL 1 RA的表达而平行地缓和IL 1作用。IL 1B对IL 1 R1和IL 1 RA的调节涉及基因转录激活，而IL 1 R2的调节涉及mRNA稳定。考虑到IL 1的免疫调节、促血管生成和组织重塑特性，以及其作为胚胎信号的作用，子宫内膜细胞对IL 1的反应性通过其自身的活化和抑制受体以及受体拮抗剂的伴随调节而调节，这可能代表了IL 1的重要调节机制。在正常月经周期和胚胎发育过程中，诱导人子宫内膜发生生理变化。
Interleukin 1 (IL1) plays an important role in the physiology of human endometrium and is recognized as a major and early embryonic signal. Tight control over the local endometrial action of this cytokine is critical for normal reproductive functions. The coordinated regulation of IL1 receptors types I and II (IL1R1 and IL1R2) and IL1 receptor antagonist (IL1RA) in endometrial cells may represent one of the principle mechanisms involved in the control of IL1 local effects. The objective of this study was to investigate the regulation of IL1Rs in human endometrial epithelial cells in response to IL1.Cultures of KLE endometrial epithelial cell line and primary human endometrial epithelial cells, immunofluorescent staining, enzyme-linked immunosorbent assay, western blotting, nuclear transcription (run-on) and real-time PCR were used to investigate the expression of IL1R1, IL1R2 and IL1RA.Cells appeared to react to IL1 by up-regulating the expression of the signaling activating IL1R1 and to moderate in parallel IL1 effects by elevating the expression of the decoy inhibitory IL1R2 and the receptor antagonist IL1RA. Regulation of IL1R1 and IL1RA by IL1B involved gene transcription activation and that of IL1R2 involved mRNA stabilization.Considering IL1's immunomodulatory, proangiogenic and tissue remodeling properties, and its role as an embryonic signal, modulation of endometrial cell responsiveness to IL1 via the concomitant regulation of its own activating and inhibitory receptors and receptor antagonist may represent an important regulatory mechanism of IL1-induced physiological changes occurring in the human endometrium during the normal menstrual cycle and embryo development.