Chung H W, Wen Y, Ahn J J, Moon H S, Polan M L
Department of Gynecology and Obstetrics, Stanford University School of Medicine, California 94305-5317, USA.
J Clin Endocrinol Metab. 2001 Mar;86(3):1332-40. doi: 10.1210/jcem.86.3.7335.
The interleukin-1 (IL-1) system plays an integral role in local intercellular interactions during implantation. In addition, the plasminogen activator system, especially urokinase plasminogen activator (u-PA), plasminogen activator inhibitor (PAI-1), and u-PA receptor (u-PAR), are crucial during embryo implantation. Decidualization and implantation are complex processes dependent upon several proteases, including u-PA, and IL-1 is known to affect PA activity in several cell types. We investigated the role of IL-1beta in regulating u-PA, PAI-1, u-PAR, and soluble u-PAR messenger ribonucleic acid (mRNA) expression in cultured human endometrial stromal cells using quantitative competitive PCR. For confirmation of the mRNA data, we measured PAI-1 and u-PAR protein by enzyme-linked immunosorbent assay. Confluent stromal cell cultures treated with progesterone and estradiol for 9 days were stimulated with IL-1beta, and IL-1beta plus IL-1beta antibody for an additional 24 h. Total RNA was extracted, reverse transcribed, and coamplified using quantitative and competitive PCR with internal standards. IL-1beta increased PAI-1, u-PAR, and soluble u-PAR expression in a dose-dependent manner, and this result was reversed by anti-IL-1beta antibody treatment. u-PA mRNA expression was not dependent on IL-1beta. These results suggest that IL-1 may be important in regulating PAI-1 and u-PAR during stromal cell decidualization before implantation.
白细胞介素-1(IL-1)系统在着床过程中的局部细胞间相互作用中起着不可或缺的作用。此外,纤溶酶原激活物系统,尤其是尿激酶型纤溶酶原激活物(u-PA)、纤溶酶原激活物抑制剂(PAI-1)和u-PA受体(u-PAR),在胚胎着床过程中至关重要。蜕膜化和着床是依赖于多种蛋白酶的复杂过程,其中包括u-PA,并且已知IL-1会影响多种细胞类型中的PA活性。我们使用定量竞争性PCR研究了IL-1β在调节培养的人子宫内膜基质细胞中u-PA、PAI-1、u-PAR和可溶性u-PAR信使核糖核酸(mRNA)表达中的作用。为了证实mRNA数据,我们通过酶联免疫吸附测定法测量了PAI-1和u-PAR蛋白。用孕酮和雌二醇处理9天的汇合基质细胞培养物用IL-1β以及IL-1β加IL-1β抗体再刺激24小时。提取总RNA,进行逆转录,并使用带有内标的定量和竞争性PCR进行共扩增。IL-1β以剂量依赖性方式增加PAI-1、u-PAR和可溶性u-PAR的表达,并且抗IL-1β抗体处理可逆转这一结果。u-PA mRNA表达不依赖于IL-1β。这些结果表明,IL-1在着床前基质细胞蜕膜化过程中调节PAI-1和u-PAR可能很重要。