Tumour necrosis factor-α up-regulates macrophage migration inhibitory factor expression in endometrial stromal cells via the nuclear transcription factor NF-κB
Tumour necrosis factor-α up-regulates macrophage migration inhibitory factor expression in endometrial stromal cells via the nuclear transcription factor NF-κB
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DOI：
10.1093/humrep/dei315
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发表时间：
2006-02-01
影响因子：
6.1
通讯作者：
Akoum, A
中科院分区：
文献类型：
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作者：
Cao, WG;Morin, M;Akoum, A
背景：在每个正常的月经周期中，人子宫内膜发生增殖、分泌和月经脱落等一系列可控变化。巨噬细胞迁移抑制因子（Macrophage migration inhibitory factor， MIF）是一种具有多种促炎、免疫调节和血管生成特性的多功能细胞因子，似乎在人子宫内膜中表达，并遵循受调节的周期相依赖性表达，但子宫内膜MIF表达的机制仍未完全阐明。方法和结果：酶联免疫吸附试验（ELISA）结果显示，人子宫内膜细胞对肿瘤坏死因子- α (tnf - α) （0.1-100 ng/ml）的反应，MIF分泌显著的剂量和时间依赖性增加。通过逆转录(RT)-PCR，在mRNA水平上也观察到这种增加。姜黄素（10(-8)mol/l）是一种已知的核因子(NF)-kappa B抑制剂，通过western blotting、电泳迁移量转移实验、ELISA和RT-PCR检测，姜黄素可抑制tnf α诱导的pI -kappa B磷酸化、NF-kappa B向细胞核内易位、MIF合成和分泌。通过瞬时细胞转染分析，显性阴性NF-kappa B抑制剂（I kappa B）的表达显著降低了tnf - α诱导的MIF启动子活性。结论：这些结果清楚地表明，tnf - α上调子宫内膜间质细胞中MIF的表达。这可能是通过nf - κ B激活发生的，并可能在人类子宫内膜的生理学中发挥重要作用。
BACKGROUND: A series of controlled changes including proliferation, secretion and menstrual shedding occur in the human endometrium during every normal menstrual cycle. Macrophage migration inhibitory factor (MIF), a multifunctional cytokine with numerous proinflammatory, immunomodulatory and angiogenic properties, appears to be expressed in the human endometrium and to follow a regulated cycle phase-dependent expression, but the mechanisms underlying endometrial MIF expression remain to be fully elucidated. METHODS AND RESULTS: Results from enzyme-linked immunosorbent assay (ELISA) demonstrated a significant dose- and time-dependent increase in MIF secretion by human endometrial cells in response to tumour necrosis factor-alpha (TNF-alpha) (0.1-100 ng/ml). This increase was also observed at the mRNA level as shown by reverse transcription (RT)-PCR. Curcumin (10(-8) mol/l), a known nuclear factor (NF)-kappa B inhibitor, inhibited the TNF-alpha-induced pI kappa B phosphorylation as shown by western blotting, NF-kappa B translocation into the nucleus as shown by electrophoretic mobility shift assay, and MIF synthesis and secretion as measured by ELISA and RT-PCR. The expression of a dominant-negative NF-kappa B inhibitor (I kappa B) significantly decreased the TNF-alpha-induced MIF promoter activity as analysed by transient cell transfection. CONCLUSIONS: These results indicate clearly that TNF-alpha up-regulates the expression of MIF in endometrial stromal cells. This took place possibly through NF-kappa B activation, and may play an important role in the physiology of the human endometrium.