期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 185, 期 5, 页码 1334-1343出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2015.01.019
关键词
-
类别
资金
- Austrian Science Fund [P23859-B19]
- Deutsche Forschungsgemeinschaft [HE6249/1-1]
- Austrian Science Fund (FWF) [P23859] Funding Source: Austrian Science Fund (FWF)
- Austrian Science Fund (FWF) [P 23859] Funding Source: researchfish
The pathogenesis of preeclampsia (PE) includes the release of placental factors into the maternal circulation, inducing an inflammatory environment in the mother. One of the factors may be the proinflammatory chemokine fractalkine, which is expressed in the syncytiotrophoblast of human placenta, from where it is released into the maternal circulation by constitutive shedding. We examined whether placental fractalkine is up-regulated in severe early-onset PE and whether the proinflammatory cytokines tumor necrosis factor (TNF)-alpha and IL-6 are able to increase the expression of fractalkine. Gene expression analysis, enzyme-linked immunosorbent assay, and immunohistochemistry consistently showed increased fractalkine expression in placentas from severe early-onset PE, compared to gestational age-matched controls. Expression of a disintegrin and metalloproteinases (ADAMs) 10 and 17, which convert transmembrane fractalkine into the soluble form, was significantly increased in these cases. Incubation of first-trimester placental explants with TNF-alpha provoked a significant increase in fractalkine expression and release of the soluble form, whereas IL-6 had no effect. TNF-alpha-mediated up-regulation of placental fractalkine was reversed in the presence of the aspirin-derivative salicylate, which impaired activation of NF-kappa B p65 in TNF-alpha-treated explants. On the basis of data from placental explants, we suggest that increased maternal TNF-alpha may up-regulate the expression and release of placental fractalkine, which, in turn, may contribute to an exaggerated systemic inflammatory response in PE.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据