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Placental fractalkine is up-regulated in severe early-onset preeclampsia

Item Type:Article
Title:Placental fractalkine is up-regulated in severe early-onset preeclampsia
Creators Name:Siwetz, M. and Dieber-Rotheneder, M. and Cervar-Zivkovic, M. and Kummer, D. and Kremshofer, J. and Weiss, G. and Herse, F. and Huppertz, B. and Gauster, M.
Abstract: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 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.
Keywords:Chemokine CX3CL1, Enzyme-Linked Immunosorbent Assay, Gene Expression Profiling, Immunohistochemistry, Interleukin-6, Placenta, Pre-Eclampsia, Pregnancy, Reverse Transcriptase Polymerase Chain Reaction, Transcriptome, Tumor Necrosis Factor-{alpha}, Up-Regulation, Western Blotting
Source:American Journal of Pathology
ISSN:0002-9440
Publisher:Elsevier (U.S.A.)
Volume:185
Number:5
Page Range:1334-1343
Date:May 2015
Official Publication:https://doi.org/10.1016/j.ajpath.2015.01.019
PubMed:View item in PubMed

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