White Christine A, Dimitriadis Evdokia, Sharkey Andrew M, Stoikos Chelsea J, Salamonsen Lois A
Prince Henry's Institute of Medical Research, P.O. Box 5152, Clayton, Vic. 3168, Australia.
J Reprod Immunol. 2007 Feb;73(1):28-38. doi: 10.1016/j.jri.2006.05.003. Epub 2006 Jul 24.
Blastocyst implantation is dependent on the differentiation of endometrial stromal cells (ESC) into decidual cells. Decidualization of human ESC in vitro is enhanced by interleukin 11 (IL11), with associated changes in gene expression. Genes downstream of IL11 may provide targets for the treatment of implantation failure or the development of non-hormonal contraceptives. This study aimed to examine the effect of IL11 on interleukin 1 beta (IL1B) mRNA and protein expression during in vitro decidualization of ESC. Cells were decidualized with 17beta-estradiol and medroxyprogesterone acetate in the presence or absence of exogenous IL11, and IL1B mRNA was quantified by real-time RT-PCR. Inactive proIL1B and bioactive IL1B in cell lysates and conditioned media were measured using specific immunoassays. Secretion of bioactive IL1B from decidualizing ESC was investigated by in vitro stimulation of decidualizing cells with lipopolysaccharide, interferon gamma or human chorionic gonadotropin. Immunohistochemistry was carried out on cycling and pregnant decidua using an antibody specific for bioactive IL1B. Exogenous IL11 increased by 28-fold the abundance of IL1B mRNA in decidualizing ESC, and total immunoreactive IL1B was also increased. However, this was not reflected in bioactive IL1B secretion from these cells, and none of the tested stimuli were able to induce its release. Bioactive IL1B was detected in vivo at very low levels and at discrete foci in late secretory phase and first trimester decidua. This regulation of latent and bioactive IL1B at the fetal-maternal interface may prime decidual cells to respond rapidly to immunological challenge or to signals from the blastocyst during implantation.
囊胚着床依赖于子宫内膜基质细胞（ESC）分化为蜕膜细胞。白细胞介素11（IL11）可增强人ESC在体外的蜕膜化，并伴有基因表达的相关变化。IL11下游的基因可能为治疗着床失败或开发非激素避孕药提供靶点。本研究旨在检测IL11对ESC体外蜕膜化过程中白细胞介素1β（IL1B）mRNA和蛋白表达的影响。在有或无外源性IL11的情况下，用17β-雌二醇和醋酸甲羟孕酮使细胞蜕膜化，通过实时RT-PCR定量IL1B mRNA。使用特异性免疫测定法测量细胞裂解物和条件培养基中的无活性前体IL1B和生物活性IL1B。通过用脂多糖、干扰素γ或人绒毛膜促性腺激素体外刺激蜕膜化细胞，研究蜕膜化ESC分泌生物活性IL1B的情况。使用针对生物活性IL1B的特异性抗体对周期性和妊娠蜕膜进行免疫组织化学分析。外源性IL11使蜕膜化ESC中IL1B mRNA的丰度增加了28倍，总免疫反应性IL1B也增加。然而，这并未反映在这些细胞分泌的生物活性IL1B中，且所测试的刺激物均不能诱导其释放。在体内，生物活性IL1B在分泌晚期和孕早期蜕膜中的水平非常低且呈离散灶性分布。胎儿-母体界面处潜在和生物活性IL1B的这种调节可能使蜕膜细胞在着床期间对免疫挑战或来自囊胚的信号迅速做出反应。
