Induction of an angiogenic phenotype in endometriotic stromal cell cultures by interleukin-1β
Induction of an angiogenic phenotype in endometriotic stromal cell cultures by interleukin-1β
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DOI：
10.1093/molehr/6.3.269
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发表时间：
2000-03-01
影响因子：
4
通讯作者：
Taylor, RN
中科院分区：
文献类型：
--
作者：
Lebovic, DI;Bentzien, F;Taylor, RN
活化的腹腔巨噬细胞与子宫内膜异位症相关，并可能通过释放白细胞介素-1 β（IL-1 β）应答子宫内膜反流而在其病因学中发挥重要作用。血管供应的发展与血管移植的建立是同等重要的。在这项研究中，我们研究了两种子宫内膜蛋白，血管内皮生长因子（VEGF）和白细胞介素-6（IL-6）的血管生成特性，并评估了它们在从正常子宫内膜（NE）和子宫内膜异位病变（EI）分离的人基质细胞中对IL-1 β刺激的反应，用[H-3]-胸苷掺入法观察VEGF对牛脑毛细血管内皮细胞（BBCE）增殖的影响。相对于盐水处理的对照培养物，在体外添加VEGF和IL-6（2.1 +/-0.2倍; P < 0.05）或VEGF和IL-6（1.8 +/-0.1倍; P < 0.05）。北方印迹分析显示，IL-1 β诱导EI细胞VEGF mRNA（2.6倍; P < 0.05）和IL-6 mRNA（6.3倍; P < 0.05）转录，但不诱导NE细胞。在应答EI细胞中，VEGF和IL-6蛋白分泌也观察到类似的诱导。I型IL-1受体（IL-1 RI）的逆转录-聚合酶链反应（RT-PCR）表明，IL-1 β对NE和EI细胞的不同作用与EI细胞中比NE细胞多2.4 +/- 0.1倍的受体mRNA相关。我们认为IL-1 β激活EI基质细胞而非NE细胞中血管生成表型的能力是由IL-1 RI介导的。
Activated peritoneal macrophages are associated with endometriosis and may play a central role in its aetiology by releasing interleukin-1 beta (IL-1 beta) in response to refluxed endometrium. Pari passu with the establishment of endometriotic implants is the development of a vascular supply. In this study we investigated the angiogenic properties of two endometrial proteins, vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6), and assessed their production in response to IL-1 beta stimulation in human stromal cells isolated from normal endometrium (NE) and endometriotic lesions (EI), Proliferation of bovine brain capillary endothelial cells (BBCE) with a [H-3]-thymidine incorporation assay was observed when VEGF (2.1 +/- 0.2-fold; P < 0.05) or VEGF and IL-6 (1.8 +/- 0.1-fold; P < 0.05) were added in vitro, relative to saline-treated control cultures. Northern blot analysis showed induction of VEGF mRNA (2.6-fold; P < 0.05) and IL-6 mRNA (6.3-fold; P < 0.05) transcripts in EI cells, but not NE cells, exposed to IL-1 beta. A similar induction was seen with VEGF and IL-6 protein secretion in the responsive EI cells. Reverse transcription-polymerase chain reaction (RT-PCR) for the IL-1 receptor type I (IL-1 RI) indicated that the differential effects of IL-1 beta on NE and EI cells was associated with 2.4 +/- 0.1-fold more receptor mRNA in EI versus NE cells. We propose that the ability of IL-1 beta to activate an angiogenic phenotype in EI stromal cells but not in NE cells, is mediated by the IL-1 RI.