Neuromedin B mediates IL-6 and COX-2 expression through NF-κB/P65 and AP-1/C-JUN activation in human primary myometrial cells
Neuromedin B mediates IL-6 and COX-2 expression through NF-κB/P65 and AP-1/C-JUN activation in human primary myometrial cells
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Neuromedin B 通过人原代子宫肌细胞中 NF-κB/P65 和 AP-1/C-JUN 激活介导 IL-6 和 COX-2 表达
DOI：
10.1042/bsr20192139
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发表时间：
2019-10
影响因子：
4
通讯作者：
张卫社
中科院分区：
文献类型：
--
作者：
朱特选;陈景飞;张卫社
摘要神经梅毒素B(NMB)及其受体通过介导炎性因子调节临产，但其内在机制尚不清楚。本研究旨在探讨NMB诱导人原代子宫肌层细胞环氧合酶-2(COX-2)表达和IL-6产生的机制。结果表明，NMB可增加核因子κB(NF-κB)转录因子p65(P65)和原癌基因jun、激活蛋白1(AP-1)转录因子亚单位(c-jun)的磷酸化，进而显著上调COX-2和IL-6的表达水平。这种上调可被p65或c-jun基因敲除后显著减弱，而被p65或c-jun基因过度表达所增强。此外，我们还发现在刺激NMB后p65和c-jun之间存在潜在的相互作用。P65磷酸化水平与COX-2、IL-6水平呈显著正相关，c-jun磷酸化水平与COX-2、IL-6水平呈显著正相关。以上结果提示，NMB诱导的COX-2和IL-6的表达是通过p65和c-jun的激活来实现的。
Abstract Neuromedin B (NMB) and its receptor regulate labor onset by mediating inflammatory factors; however the underlying mechanisms remain poorly understood. The present study is aimed to investigate the mechanisms of NMB-induced cyclo-oxygenase 2 (COX-2) expression and interleukin (IL)-6 generation in human primary myometrial cells. The results indicated that NMB could increase phosphorylation of nuclear factor κB (NF-κB) transcription factor p65 (p65) and Jun proto-oncogene, activator protein 1 (AP-1) transcription factor subunit (c-Jun), and in turn, markedly up-regulated the expression levels of COX-2 and IL-6. This up-regulation was significantly attenuated by knockdown of p65 or c-Jun, and enhanced by overexpression of p65 or c-Jun. Furthermore, we identified a potential interaction between p65 and c-Jun following NMB stimulation. In addition, a significant positive correlation was observed between the amount of phosphorylated p65 and the levels of COX-2 and IL-6, and between the amount of phosphorylated c-Jun and COX-2 and IL-6 levels. These data suggested that NMB-induced COX-2 and IL-6 expression were mediated via p65 and c-Jun activation.
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影响因子：
6
作者：
Christian F;Smith EL;Carmody RJ
通讯作者：
Carmody RJ
影响因子：
3.7
作者：
Lim S;MacIntyre DA;Lee YS;Khanjani S;Terzidou V;Teoh TG;Bennett PR
通讯作者：
Bennett PR
影响因子：
4.6
作者：
Khanjani S;Terzidou V;Johnson MR;Bennett PR
通讯作者：
Bennett PR
影响因子：
3.8
作者：
J. Challis;D. Sloboda;N. Alfaidy;S. Lye;W. Gibb;F. Patel;W. Whittle;J. Newnham
通讯作者：
J. Challis;D. Sloboda;N. Alfaidy;S. Lye;W. Gibb;F. Patel;W. Whittle;J. Newnham
影响因子：
4
作者：
Yun‐Sil Lee;V. Terzidou;T. Lindstrom;Mark Johnson;P. Bennett
通讯作者：
Yun‐Sil Lee;V. Terzidou;T. Lindstrom;Mark Johnson;P. Bennett