Simón C, Piquette G N, Frances A, el-Danasouri I, Irwin J C, Polan M L
Department of Gynecology and Obstetrics, Stanford University Medical Center, California 94305.
J Clin Endocrinol Metab. 1994 Mar;78(3):675-82. doi: 10.1210/jcem.78.3.8126141.
Because we hypothesize that the interleukin-1 (IL-1) system may be important in the dialogue between mother and embryo during the implantation process, we have analyzed the effect of IL-1 beta, a secretory product of the human embryo and human endometrium, on the mRNA and protein levels of IL-1 receptor type I (IL-1R tI) in the human endometrium. For this purpose, endometrial epithelial cells (EEC) and stromal cells (ESC) were isolated and cultured with progesterone (3.18 micrograms/mL) and epidermal growth factor (20 ng/mL) for 8 days in the presence or absence of hrIL-1 beta (20 pg/mL). EEC from proliferative and secretory endometrium expressed high levels of IL-1R tI mRNA compared to ESC, and these levels were not modulated by IL-1 beta. However, prostaglandin E2 levels peaked on day 4 in EEC treated with progesterone, epidermal growth factor, and IL-1 beta (208.7 +/- 92 ng/10(7) cells), whereas no prostaglandin E2 was detectable in cells not treated with IL-1 beta, indicating that these cells responded to IL-1 beta. With regard to ESC from secretory endometrium, IL-1 beta increased its own receptor mRNA levels (4 +/- 0.5-fold increase) after 8 days in culture. However, when ESC were isolated from proliferative endometrium, an up-regulation of IL-1R tI (3.5 +/- 0.5-fold increase) was observed on days 6 and 8 of culture regardless of the presence or absence of IL-1 beta. Immunoreactive IL-1R tI was identified in cultured EEC and ESC, and patterns similar to those of mRNA were observed. The constitutive presence of IL-1R tI in EEC, which was not affected by IL-1 beta, and the up-regulation of IL-1R tI mRNA by its ligand IL-1 beta in ESC isolated during the luteal phase suggest a role for the IL-1 system in human implantation.
因为我们假设白细胞介素-1(IL-1)系统在植入过程中母体与胚胎之间的对话中可能很重要,所以我们分析了人胚胎和人子宫内膜的分泌产物IL-1β对人子宫内膜中I型IL-1受体(IL-1R tI)的mRNA和蛋白水平的影响。为此,分离出子宫内膜上皮细胞(EEC)和基质细胞(ESC),在存在或不存在重组人IL-1β(20 pg/mL)的情况下,用孕酮(3.18微克/毫升)和表皮生长因子(20纳克/毫升)培养8天。与ESC相比,增殖期和分泌期子宫内膜的EEC表达高水平的IL-1R tI mRNA,且这些水平不受IL-1β调节。然而,在用孕酮、表皮生长因子和IL-1β处理的EEC中,前列腺素E2水平在第4天达到峰值(208.7±92纳克/10⁷个细胞),而在未用IL-1β处理的细胞中未检测到前列腺素E2,这表明这些细胞对IL-1β有反应。关于分泌期子宫内膜的ESC,培养8天后,IL-1β增加了其自身受体mRNA水平(增加4±0.5倍)。然而,当从增殖期子宫内膜分离ESC时,无论是否存在IL-1β,在培养的第6天和第8天均观察到IL-1R tI上调(增加3.5±0.5倍)。在培养的EEC和ESC中鉴定出免疫反应性IL-1R tI,并且观察到与mRNA相似的模式。EEC中IL-1R tI的组成性存在不受IL-1β影响,而在黄体期分离的ESC中其配体IL-1β使IL-1R tI mRNA上调,这表明IL-1系统在人类植入过程中起作用。