Preeclampsia Status Controls Interleukin-6 and Soluble IL-6 Receptor Release from Neutrophils and Endothelial Cells: Relevance to Increased Inflammatory Responses.

Preeclampsia Status Controls Interleukin-6 and Soluble IL-6 Receptor Release from Neutrophils and Endothelial Cells: Relevance to Increased Inflammatory Responses.
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先兆子痫状态控制白介素6和可溶性IL-6受体从中性粒细胞和内皮细胞释放:与炎症反应增加有关。

DOI:
10.3390/pathophysiology28020013
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发表时间:
2021-04-08
期刊:
Pathophysiology : the official journal of the International Society for Pathophysiology
影响因子:
--
通讯作者:
Lewis DF
Lewis DF
中科院分区:
其他
文献类型:
--
作者:
Wang Y;Gu Y;Alexander JS;Lewis DF

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在人类妊娠期高血压疾病先兆子痫中,嗜酸性粒细胞-内皮细胞结合和炎症反应的增加是母体血管系统中的重要病理生理事件。白细胞介素6(IL-6)及其可溶性受体(可溶性IL-6 R(sIL-6 R)和可溶性gp 130(sgp 130))是重要的炎症介质。在妊娠期间,与血压正常的孕妇相比,先兆子痫孕妇的母体IL-6和sgp 130水平升高,但sIL-6 R水平降低。然而,很少有人知道正常妊娠和先兆子痫之间的中性粒细胞和内皮细胞的IL-6,sIL-6 R和sgp 130生产的差异。为了研究这一点,我们分离中性粒细胞和培养人脐静脉内皮细胞(HUVECs)从正常和先兆子痫妊娠。测定IL-6、sIL-6 R和sgp 130的产生。胎盘因子介导的中性粒细胞产生IL-6、sIL-6 R和sgp 130的作用也通过用胎盘绒毛培养物产生的胎盘条件培养基预处理中性粒细胞来确定。IL-6和sgp 130主要由内皮细胞产生,而sIL-6 R主要由中性粒细胞产生。先兆子痫患者的内皮细胞产生的IL-6和sgp 130显著高于正常妊娠细胞,而先兆子痫患者的中性粒细胞产生的sIL-6 R显著低于正常妊娠细胞。有趣的是,当中性粒细胞和内皮细胞共培养时,IL-6、sIL-6 R和sgp 130的产生呈时间依赖性增加。我们还发现,正常妊娠的中性粒细胞产生更多的IL-6,但较少的sIL-6 R后,被引发的先兆子痫胎盘条件培养基。这些结果表明,中性粒细胞和内皮细胞产生IL-6,sIL-6 R,和sgp 130的能力在正常妊娠和先兆子痫之间有不同。这些结果也提供了证据,胎盘在诱导先兆子痫中性粒细胞活化中起作用。
Increased neutrophil–endothelial binding and inflammatory responses are significant pathophysiological events in the maternal vascular system in preeclampsia, a hypertensive disorder in human pregnancy. Interleukin 6 (IL-6) and its soluble receptors (soluble IL-6R (sIL-6R) and soluble gp130 (sgp130)) are critical inflammatory mediators. During pregnancy, maternal IL-6 and sgp130 levels were increased, but sIL-6R levels were decreased, in women with preeclampsia compared to normotensive pregnant women. However, little is known about differences in IL-6, sIL-6R, and sgp130 production by neutrophils and endothelial cells between normal pregnancy and preeclampsia. To study this, we isolated neutrophils and cultured human umbilical vein endothelial cells (HUVECs) from normal and preeclamptic pregnancies. Production of IL-6, sIL-6R, and sgp130 was measured. The role of placental factor(s)-mediated neutrophil production of IL-6, sIL-6R, and sgp130 was also determined by pretreating neutrophils with placental conditioned medium generated from placental villous cultures. We found that IL-6 and sgp130 were mainly produced by endothelial cells, while sIL-6R was mainly produced by neutrophils. Endothelial cells from preeclampsia produced significantly more IL-6 and sgp130, and neutrophils from preeclampsia produced significantly less sIL-6R than normal pregnancy cells. Interestingly, production of IL-6, sIL-6R, and sgp130 were time-dependently increased when neutrophils and endothelial cells were co-cultured. We also found that neutrophils from normal pregnancies produced more IL-6, but less sIL-6R, after being primed by preeclamptic-placental conditioned medium. These results demonstrated that neutrophils and endothelial cells have different capacities in producing IL-6, sIL-6R, and sgp130 between normal pregnancy and preeclampsia. These results also provide evidence that the placenta plays a role in inducing neutrophil activation in preeclampsia.
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发表时间: 2001-01-01
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影响因子: --
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