title: Hypoxia-Mediated Soluble Fms-Like Tyrosine Kinase 1 Increase Is Not Attenuated in Interleukin 6-Deficient Mice.
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.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany sarah.appel@uk-koeln.de.
authors.forename: Sarah
authors.initials: S
authors.lastname: Appel
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Turnwald
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Ankerne
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Wohlfarth
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Appel
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Rother
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Janoschek
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Alejandre Alcazar
authors.affiliation: Institute for Immunology, University of Marburg, Marburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schnare
authors.affiliation: Hainstrasse 20, 96047 Bamberg, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Meißner
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Dötsch
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005865:Gestational Age; D000860:Hypoxia / Q000097:blood / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010920:Placenta / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D015854:Up-Regulation; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood* / Q000235:genetics
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015850:Interleukin-6; C577686:interleukin-6, mouse; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: hypoxia; placenta; sFlt-1