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Hypoxia-Mediated Soluble Fms-Like Tyrosine Kinase 1 Increase Is Not Attenuated in Interleukin 6-Deficient Mice

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Abstract

The soluble fms-like tyrosine kinase 1 (sFlt-1), known to be increased in the serum of preeclamptic patients, is a relevant factor in causing maternal symptoms like hypertension and proteinuria. In this study, we aimed to reveal whether hypoxia is a cause of increased sFlt-1 levels and inflammation markers in vivo and whether these symptoms can be attenuated by interleukin 6 (IL-6) depletion. For this purpose, pregnant wild-type (wt) mice or IL-6−/− mice on embryonic day 16 were placed under either normoxic (20.9% oxygen) or hypoxic (6% oxygen) conditions for 6 hours. This led to a rise of sFlt-1 levels in maternal serum, independent of the IL-6 status of the dam. Increased maternal sFlt-1 serum levels were, however, not due to an increase in sFlt-1 messenger RNA levels in the placenta. Moreover, there was no increase in inflammatory markers in neither wt mice nor IL-6−/− mice. This suggests that hypoxia alone does not contribute to the induction of an inflammatory placenta. Also, the hypoxia-induced rise in sFlt-1 levels seems not to be mediated by IL-6 in vivo.

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Authors and Affiliations

  1. Department of Pediatrics and Adolescent Medicine, University of Cologne, Robert Koch Str. 16, 50931, Cologne, Germany

    Sarah Appel Dr. rer. nat., Eva-Maria Turnwald, Janina Ankerne, Maria Wohlfarth, Jan Appel, Eva Rother Dr. med., Dr. nat. med., Ruth Janoschek Dr. rer. nat., Miguel A. Alejandre Alcazar Dr. med., Dr. nat. med. & Jörg Dötsch Prof. Dr. med.

  2. Institute for Immunology, University of Marburg, Marburg, Germany

    Markus Schnare Prof. Dr. rer. physiol.

  3. Hainstrasse 20, 96047, Bamberg, Germany

    Udo Meißner Dr. med.

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  1. Sarah Appel Dr. rer. nat.
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  2. Eva-Maria Turnwald
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Correspondence to Sarah Appel Dr. rer. nat..

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Appel, S., Turnwald, EM., Ankerne, J. et al. Hypoxia-Mediated Soluble Fms-Like Tyrosine Kinase 1 Increase Is Not Attenuated in Interleukin 6-Deficient Mice. Reprod. Sci. 22, 735–742 (2015). https://doi.org/10.1177/1933719114557898

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