title: Placental fractalkine is up-regulated in severe early-onset preeclampsia.
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)-α 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-α provoked a significant increase in fractalkine expression and release of the soluble form, whereas IL-6 had no effect. TNF-α-mediated up-regulation of placental fractalkine was reversed in the presence of the aspirin-derivative salicylate, which impaired activation of NF-κB p65 in TNF-α-treated explants. On the basis of data from placental explants, we suggest that increased maternal TNF-α may up-regulate the expression and release of placental fractalkine, which, in turn, may contribute to an exaggerated systemic inflammatory response in PE.
authors.affiliation: Institute of Cell Biology, Histology and Embryology, Medical University Graz, Graz, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Siwetz
authors.affiliation: Department of Obstetrics and Gynaecology, Medical University Graz, Graz, Austria; Institute of Pathology, Medical University Graz, Graz, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Dieber-Rotheneder
authors.affiliation: Department of Obstetrics and Gynaecology, Medical University Graz, Graz, Austria.
authors.forename: Mila
authors.initials: M
authors.lastname: Cervar-Zivkovic
authors.affiliation: Institute of Cell Biology, Histology and Embryology, Medical University Graz, Graz, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kummer
authors.affiliation: Institute of Cell Biology, Histology and Embryology, Medical University Graz, Graz, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Kremshofer
authors.affiliation: Institute of Cell Biology, Histology and Embryology, Medical University Graz, Graz, Austria.
authors.forename: Gregor
authors.initials: G
authors.lastname: Weiss
authors.affiliation: Experimental and Clinical Research Center, a Joint Cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Herse
authors.affiliation: Institute of Cell Biology, Histology and Embryology, Medical University Graz, Graz, Austria.
authors.forename: Berthold
authors.initials: B
authors.lastname: Huppertz
authors.affiliation: Institute of Cell Biology, Histology and Embryology, Medical University Graz, Graz, Austria. Electronic address: martin.gauster@medunigraz.at.
authors.forename: Martin
authors.initials: M
authors.lastname: Gauster
mesh_terms: D000328:Adult; D015153:Blotting, Western; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha