Exogenous soluble VEGF receptor-1 (sFlt-1) regulates Th1/Th2 cytokine production from normal placental explants via intracellular calcium

Bei Xu, Charlene Thornton, Jane Tooher, Annemarie Hennessy

    Research output: Contribution to journalArticle

    Abstract

    The increase of soluble VEGF-Receptor 1 (sFlt-1) is thought to contribute to the pathogenesis of preeclampsia. Soluble VEGF-Receptor 1 binds to circulating free VEGF and PLGF and this cascade is associated with endothelial dysfunction, a prominent feature of preeclampsia. Preeclampsia is also associated with excessive maternal response to pro-inflammatory stimuli manifesting as an imbalance of Th1/Th2 cytokine production at the maternal-fetal interface. Whether increased sFlt-1 expression has any effect on placental production of Th1/Th2 cytokines IL-10 and TNF-a is yet to be investigated. The aim of this study is to examine if exogenous sFlt-1 can regulate Th1/Th2 cytokines IL-10 and TNF-a production from normal placental explants via intracellular calcium release. Placental explants were taken from the decidual surface of normal non-laboured term placentas (n = 11).Villous explants were cultured with increasing concentrations of sFlt-1. The dose effect of sFlt-1 on placental Th1 and Th2 cytokine production (TNF-a and IL-10) were examined. Free PLGF, VEGF and sFlt-1 concentrations in the conditioned medium were also measured. Intracellular calcium blocker, 1,2-bis-(o-aminophenoxy)-ethane-N,N,N′,N′-tetraacetic acid, tetra(acetoxymethyl)-ester (BAPTA/AM) was applied to investigate whether the changes in cytokine concentration were mediated by intracellular free calcium. Results: Placental IL-10 and TNF-a production were significantly increased after sFlt-1 incubation. The increase in IL-10 can be inhibited by BAPTA/AM. Soluble Flt-1 and free PLGF concentration in the conditioned medium was not changed. Free VEGF concentration in the conditioned medium was not detectable. Exogenous sFlt-1 can increase TNF-a and IL-10 production from normal placental explants. The change in Th1/Th2 cytokine level may be mediated by intracellular free calcium.
    Original languageEnglish
    Pages (from-to)448-456
    Number of pages8
    JournalHypertension in Pregnancy
    Volume28
    Issue number4
    Publication statusPublished - 2009

    Keywords

    • cytokines
    • intracellular calcium
    • placenta
    • preeclampsia
    • soluble VEGF-Receptor 1
    • vascular endothelial growth factors

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