Normoxic induction of the hypoxic-inducible factor-1 alpha by interleukin-1 beta involves the extracellular signal-regulated kinase 1/2 pathway in normal human cytotrophoblast cells. | Academic Article individual record

During early pregnancy, an environment of relative low oxygen tension is essential for normal embryonic and placental vasculature. In low-oxygen conditions, the hypoxic-inducible factor-1 (HIF-1), composed of alpha and beta subunits, controls the expression of a number of genes such as vascular endothelial growth factor (VEGF), a key angiogenic factor. The recent studies in some tumor cells have found that the labile component, HIF-1 alpha, is not only activated by hypoxia but also by peptides such as interleukin-1 (IL-1) in normoxia. In this article, we demonstrated that exposure of normal human cytotrophoblast cells to IL-1 beta stimulated the expression of HIF-1 alpha protein. Meanwhile, IL-1 beta also induced the secretion of VEGF in normal human cytotrophoblast cells. Our data indicated that IL-1 beta induced extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. Moreover, treatment of cells with PD98059, an inhibitor of ERK1/2 signaling, inhibited the stimulation of HIF-1 alpha protein expression and VEGF secretion by IL-1 beta. These data indicate that, in normal human cytotrophoblast cells, IL-1 beta induces HIF- 1 alpha-mediated VEGF secretion and that IL-1 beta-stimulated ERK1/2 activation may be involved in this process.

author list (cited authors)
Qian, D., Lin, H., Wang, H., Zhang, X., Liu, D., Li, Q., & Zhu, C.
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  • Trophoblasts
  • Flavonoids
  • Base Sequence
  • Hypoxia-Inducible Factor 1, Alpha Subunit
  • DNA
  • RNA, Messenger
  • Interleukin-1
  • Pregnancy
  • Vascular Endothelial Growth Factor A
  • Humans
  • Mitogen-Activated Protein Kinase 3
  • Enzyme Activation
  • Transcription Factors
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Female
  • Mitogen-Activated Protein Kinase 1
  • Hypoxia-Inducible Factor 1
  • In Vitro Techniques
  • MAP Kinase Signaling System
  • Enzyme Inhibitors
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