Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Base Sequence
-
DNA / genetics
-
DNA-Binding Proteins / biosynthesis*
-
DNA-Binding Proteins / genetics
-
Enzyme Activation / drug effects
-
Enzyme Inhibitors / pharmacology
-
Female
-
Flavonoids / pharmacology
-
Humans
-
Hypoxia-Inducible Factor 1
-
Hypoxia-Inducible Factor 1, alpha Subunit
-
In Vitro Techniques
-
Interleukin-1 / pharmacology*
-
MAP Kinase Signaling System / drug effects
-
Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
-
Mitogen-Activated Protein Kinase 1 / metabolism*
-
Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
-
Mitogen-Activated Protein Kinase 3 / metabolism*
-
Nuclear Proteins / biosynthesis*
-
Nuclear Proteins / genetics
-
Pregnancy
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
Transcription Factors / biosynthesis*
-
Transcription Factors / genetics
-
Trophoblasts / cytology
-
Trophoblasts / drug effects*
-
Trophoblasts / metabolism*
-
Vascular Endothelial Growth Factor A / metabolism
Substances
-
DNA-Binding Proteins
-
Enzyme Inhibitors
-
Flavonoids
-
HIF1A protein, human
-
Hypoxia-Inducible Factor 1
-
Hypoxia-Inducible Factor 1, alpha Subunit
-
Interleukin-1
-
Nuclear Proteins
-
RNA, Messenger
-
Transcription Factors
-
Vascular Endothelial Growth Factor A
-
DNA
-
Mitogen-Activated Protein Kinase 1
-
Mitogen-Activated Protein Kinase 3
-
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one