The NF-κB pathway in human endometrium and first trimester decidua
The NF-κB pathway in human endometrium and first trimester decidua
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DOI：
10.1093/molehr/7.2.175
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发表时间：
2001-02-01
影响因子：
4
通讯作者：
Kelly, RW
中科院分区：
文献类型：
--
作者：
King, AE;Critchley, HOD;Kelly, RW
核因子-kappaB(NF-kappaB)调节致炎基因，可能参与月经、着床等生殖相关的炎症反应。核因子-kappaB的激活涉及几种蛋白激酶和随后内源性抑制物I-kappaBα的降解，本研究详细介绍了核因子-kappaB途径中间产物在人子宫内膜和早孕蜕膜中的表达，检测了I-kappaBα的信使RNA，I-kappaB-Gamma(一种支架蛋白)和蛋白激酶、ikk-α、ikk-β、NF-kappaB诱导激酶(Nik)、丝裂原活化的蛋白激酶Erk-Kinase 1(MEKK1)和坦克结合激酶1(TBK1)在月经周期的周围阶段，提示在绝经前停用孕酮后，可能存在着核因子-kappaB的激活，因为核因子-kappaB的活性增加了I-kappaBα基因的表达。早孕时，随着孕酮浓度的升高，NF-kappaB途径中间产物的表达出现差异；蜕膜中IKKα和Nik的mRNA水平增加，而ikkβ和MEKK1的mRNA水平下降。免疫组织化学方法检测IKKα和NiK蛋白的表达谱。在子宫内膜腺上皮和内皮细胞中均有表达，在蜕膜中均有表达，在上皮和蜕膜基质细胞中均有表达。本研究结果提示，核因子-kappaB在月经期间被激活。在妊娠早期，核因子-kappaB也可能被激活(通过ikkα-Nik)，并可能调节着床和成功怀孕所必需的分子的表达。然而，对核因子-kappaB的促炎信号(通过IKKβ-MEKK1)可能在怀孕早期下调，导致此时盛行的免疫抑制机制。
Nuclear factor kappa B (NF-kappaB) regulates proinflammatory genes and may be involved in inflammation associated with reproductive events e,g. menstruation, implantation. Activation of NF-kappaB involves several protein kinases and subsequent degradation of an endogenous inhibitor, I kappaB alpha, This study details expression of NF-kappaB pathway intermediates in human endometrium and first trimester decidua, Messenger RNA was detected for I kappaB alpha, and I kappaB kinase gamma (IKK gamma, a scaffolding protein) and the protein kinases, IKK alpha, IKK beta, NF-kappaB inducing kinase (NIK), mitogenactivated protein kinase Erk kinase kinase 1 (MEKK1) and TANK-binding kinase 1 (TBK1) using real-time quantitative polymerase chain reaction (PCR), I kappaB alpha and TBK1 mRNA were increased in the perimenstrual phase of the menstrual cycle, This suggests that there is activation of NF-kappaB due to premenstrual progesterone withdrawal, since NF-kappaB activity increases I kappaB alpha gene expression. Differential expression of NF-kappaB pathway intermediates occurred when progesterone concentrations increased in early pregnancy; IKK alpha and NIK mRNA levels increased in decidua whilst IKK beta and MEKK1 mRNA levels declined. Expression profiles of IKK alpha and NIK proteins were determined immunohistochemically. Both were detected in glandular epithelium and endothelium of endometrium, In decidua, both were present in epithelium and decidualized stromal cells. The results of this study suggest that NF-kappaB is activated during menstruation. During early pregnancy, NF-kappaB may also be activated (via IKK alpha -NIK) and may regulate the expression of molecules vital for implantation and successful pregnancy. However, proinflammatory signalling to NF-kappaB (via IKK beta -MEKK1) may be down-regulated in early pregnancy, contributing to the immunosuppressive mechanisms which prevail at this time.