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

Reprod Sci. 2015 Jun;22(6):735-42. doi: 10.1177/1933719114557898. Epub 2014 Nov 18.

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.

Keywords: hypoxia; placenta; sFlt-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Gestational Age
  • Hypoxia / blood
  • Hypoxia / enzymology*
  • Hypoxia / genetics
  • Hypoxia / immunology
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Inflammation / blood
  • Inflammation / enzymology*
  • Inflammation / genetics
  • Inflammation / immunology
  • Interleukin-6 / deficiency*
  • Interleukin-6 / genetics
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Placenta / immunology
  • Placenta / metabolism
  • Pregnancy
  • Up-Regulation
  • Vascular Endothelial Growth Factor Receptor-1 / blood*
  • Vascular Endothelial Growth Factor Receptor-1 / genetics

Substances

  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Interleukin-6
  • interleukin-6, mouse
  • Flt1 protein, mouse
  • Vascular Endothelial Growth Factor Receptor-1