Nuclear factor kappa B activation occurs in the amnion prior to labour onset and modulates the expression of numerous labour associated genes.
Nuclear factor kappa B activation occurs in the amnion prior to labour onset and modulates the expression of numerous labour associated genes.
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DOI：
10.1371/journal.pone.0034707
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Bennett PR
中科院分区：
文献类型：
--
作者：
Lim S;MacIntyre DA;Lee YS;Khanjani S;Terzidou V;Teoh TG;Bennett PR
在人类分娩开始之前，在胎膜中，特别是羊膜中，有一个增加的三尖杉酯碱，细胞因子和趋化因子的合成。这与转录因子核因子κ B（NF κ B）的激活有关。在这项研究中，我们的特点是在羊膜上皮细胞的NF κ B活性水平作为羊膜激活的措施，在39周的妊娠进行剖腹产的妇女分娩前收集的样本。我们发现一部分妇女表现出低或中等水平的NF κ B活性，而其他妇女表现出高水平的NF κ B活性（n = 12）。 该活化过程似乎不涉及NF κ B活化的经典途径，而是与核p65-Rel-B二聚体的增加相关。为了鉴定与羊膜活化相关的上调的全部基因范围，对仔细表征的未活化的羊膜（n = 3）样品进行微阵列分析，并与活化的样品（n = 3）进行比较。 共有919个基因响应于羊膜活化而上调，包括许多炎性基因，如环氧合酶-2（考克斯-2，44倍）、白细胞介素8（IL-8，6倍）、IL-1受体辅助蛋白（IL-1RAP，4.5倍）、血小板反应蛋白1（TSP-1，3倍）和出乎意料的催产素受体（OTR，24倍）。微阵列数据的不稳定性途径分析揭示了与羊膜激活同时激活的两个主要基因网络是i）细胞死亡、癌症和形态学，以及ii）细胞周期、胚胎发育和组织发育。我们的研究结果表明，羊膜NF κ B活化的评估是准确的样本分类和随后的数据解释的关键。总的来说，我们的数据表明，羊膜激活在很大程度上是一种炎症事件，发生在羊膜上皮层作为分娩开始的前奏。
Prior to the onset of human labour there is an increase in the synthesis of prostaglandins, cytokines and chemokines in the fetal membranes, particular the amnion. This is associated with activation of the transcription factor nuclear factor kappa B (NFκB). In this study we characterised the level of NFκB activity in amnion epithelial cells as a measure of amnion activation in samples collected from women undergoing caesarean section at 39 weeks gestation prior to the onset of labour. We found that a proportion of women exhibit low or moderate NFκB activity while other women exhibit high levels of NFκB activity (n = 12). This activation process does not appear to involve classical pathways of NFκB activation but rather is correlated with an increase in nuclear p65-Rel-B dimers. To identify the full range of genes upregulated in association with amnion activation, microarray analysis was performed on carefully characterised non-activated amnion (n = 3) samples and compared to activated samples (n = 3). A total of 919 genes were upregulated in response to amnion activation including numerous inflammatory genes such cyclooxygenase-2 (COX-2, 44-fold), interleukin 8 (IL-8, 6-fold), IL-1 receptor accessory protein (IL-1RAP, 4.5-fold), thrombospondin 1 (TSP-1, 3-fold) and, unexpectedly, oxytocin receptor (OTR, 24-fold). Ingenuity Pathway Analysis of the microarray data reveal the two main gene networks activated concurrently with amnion activation are i) cell death, cancer and morphology and ii) cell cycle, embryonic development and tissue development. Our results indicate that assessment of amnion NFκB activation is critical for accurate sample classification and subsequent interpretation of data. Collectively, our data suggest amnion activation is largely an inflammatory event that occurs in the amnion epithelial layer as a prelude to the onset of labour.
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影响因子：
64.8
作者：
FAN, CM;MANIATIS, T
通讯作者：
MANIATIS, T
影响因子：
3.6
作者：
Ackerman, VE;Rovin, BH;Kniss, DA
通讯作者：
Kniss, DA
影响因子：
15.3
作者：
Ishikawa, H;Claudio, E;Bravo, R
通讯作者：
Bravo, R
影响因子：
64.5
作者：
HSU, HL;XIONG, J;GOEDDEL, DV
通讯作者：
GOEDDEL, DV
DOI：
10.1016/0002-9378(87)90070-6
发表时间：
1987-03-01
影响因子：
9.8
作者：
BENNETT, PR;ROSE, MP;ELDER, MG
通讯作者：
ELDER, MG