Herrmann Lavoie Catherine, Fraser Daibhid, Therriault Marie-Josée, Akoum Ali
Unité d'Endocrinologie de la Reproduction, Centre de Recherche, Hôpital Saint-François d'Assise, Centre Hospitalier Universitaire de Québec, Faculté de Médecine, Université Laval, QC, Canada.
Am J Reprod Immunol. 2007 Dec;58(6):505-13. doi: 10.1111/j.1600-0897.2007.00471.x.
Macrophage migration inhibitory factor (MIF), a potent immuno-modulatory, angiogenic and tissue remodeling factor, is markedly expressed in ectopic endometrial implants and may play key role in the capability of this tissue to grow and develop into the host tissue. The objective of this study was to determine whether macrophage-derived cytokines, such as interleukin (IL)-1, which is overproduced by endometriosis women's peritoneal macrophages and found in elevated concentration in their peritoneal fluid, may play a role in MIF synthesis and secretion by ectopic endometrial cells.
Primary cultures of endometriotic cells exposed to IL-1beta and evaluation of MIF protein by immunocytofluorescence and ELISA, and mRNA by quantitative real-time PCR and nuclear transcription assays (run-on).
Interleukin-1beta acts rapidly on endometriotic cells and stimulated MIF secretion and mRNA steady-state levels in a dose and time-dependent manner. IL-1beta treatment had no significant effect on MIF mRNA half-life and stability, but acted predominantly by up-regulating MIF gene transcription as assessed by run-on.
These data clearly indicate that IL-1 can be involved in the up-regulation of MIF expression by ectopic endometrial implants. Such an interaction between IL-1 and MIF may have an important impact on endometriotic cell growth and endometriosis pathophysiology.
巨噬细胞移动抑制因子(MIF)是一种强大的免疫调节、血管生成和组织重塑因子,在异位子宫内膜植入物中显著表达,可能在该组织生长并发展融入宿主组织的能力中起关键作用。本研究的目的是确定巨噬细胞衍生的细胞因子,如白细胞介素(IL)-1,是否会在异位子宫内膜细胞合成和分泌MIF中发挥作用。IL-1由子宫内膜异位症患者的腹膜巨噬细胞过度产生,且在其腹水中浓度升高。
将异位内膜细胞原代培养物暴露于IL-1β,通过免疫细胞荧光和酶联免疫吸附测定评估MIF蛋白,通过定量实时聚合酶链反应和核转录分析(连续转录分析)评估MIF信使核糖核酸。
白细胞介素-1β对异位内膜细胞迅速起作用,以剂量和时间依赖性方式刺激MIF分泌和信使核糖核酸稳态水平。IL-1β处理对MIF信使核糖核酸半衰期和稳定性无显著影响,但如连续转录分析所评估,主要通过上调MIF基因转录起作用。
这些数据清楚地表明,IL-1可能参与异位子宫内膜植入物对MIF表达的上调。IL-1与MIF之间的这种相互作用可能对子宫内膜异位细胞生长和子宫内膜异位症病理生理学产生重要影响。