Stimulation of macrophage migration inhibitory factor expression in endometrial stromal cells by interleukin 1, beta involving the nuclear transcription factor NFκB
Stimulation of macrophage migration inhibitory factor expression in endometrial stromal cells by interleukin 1, beta involving the nuclear transcription factor NFκB
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DOI：
10.1095/biolreprod.104.038331
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发表时间：
2005-09-01
影响因子：
3.6
通讯作者：
Akoum, A
中科院分区：
文献类型：
--
作者：
Cao, WG;Morin, M;Akoum, A
子宫内膜异位症，子宫内膜组织的异位发育，特别是在腹膜子宫内膜异位症中，被认为是由月经组织的输卵管反流引起的。回流的子宫内膜细胞对腹膜炎症刺激的反应释放细胞因子和生长因子可能增强子宫内膜细胞植入和生长到腹膜宿主组织的能力。本文中，我们报道了白细胞介素1 (IL1)，一种主要的促炎细胞因子，由子宫内膜异位症女性源性腹膜巨噬细胞过量产生，并在子宫内膜异位症患者的腹膜液中发现浓度升高，刺激人子宫内膜基质细胞巨噬细胞迁移抑制因子（MIF）的合成和分泌。ELISA和逆转录聚合酶链反应结果显示，IL1B （0.1 ~ 100 ng/ml）对MIF蛋白分泌和mRNA合成具有剂量依赖性和时间依赖性。ikappa 8磷酸化的电泳迁移率转移实验和Western blot分析显示，IL1B似乎通过kappa B核转录因子（NF kappa B）诱导MIF基因转录。姜黄素（10(-8)M）可抑制NF κ B活化，抑制il1b诱导的MIF分泌、NF κ B核易位和DNA结合。综上所述，这些研究结果清楚地表明，在体外，IL1B上调子宫内膜基质细胞中MIF的表达，并通过NF κ b起作用。考虑到MIF的免疫调节特性以及在细胞生长、血管生成和组织重塑中的作用，这可能在人子宫内膜生理学和子宫内膜异位症的病理生理中发挥重要作用。
Endometriosis, the ectopic development of endometrial tissue, is, particularly in peritoneal endometriosis, believed to result from tubal reflux of menstrual tissue. The release of cytokines and growth factors by refluxed endometrial cells in response to peritoneal inflammatory stimuli may enhance the capability of endometrial cells to implant and grow into the peritoneal host tissue. Herein we report that interleukin 1 (IL1), a major proinflammatory cytokine that is overproduced by endometriosis women-derived peritoneal macrophages and found in elevated concentrations in the peritoneal fluid of patients with endometriosis, stimulates the synthesis and the secretion of macrophage migration inhibitory factor (MIF) by human endometrial stromal cells. IL1B (0.1-100 ng/ml) exerted dose- and time-dependent effects of MIF protein secretion and mRNA synthesis, as shown by ELISA and reverse transcription-polymerase chain reaction, respectively. IL1B appeared to induce MIF gene transcription via the kappa B nuclear transcription factor (NF kappa B), as shown by electrophoretic mobility shift assay and Western blot analysis Of I kappa 8 phosphorylation. Curcumin (10(-8) M), which is known for inhibiting NF kappa B activation, inhibited IL1B-induced MIF secretion as well as NF kappa B nuclear translocation and DNA binding. Taken together, these findings clearly show that IL1B up-regulates the expression of MIF in endometrial stromal cells in vitro and acts via NF kappa B. This may play an important role in the physiology of the human endometrium and the pathophysiology of endometriosis considering the immunomodulatory properties of MIF as well as its role in cell growth, angiogenesis and tissue remodeling.