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by Interleukin-1
Involves the
Extracellular Signal-Regulated Kinase 1/2 Pathway in
Normal Human Cytotrophoblast Cells
Abstract
During early pregnancy, an environment of relative low
oxygen tension is essential for normal embryonic and
placental vasculture. In low oxygen conditions, the
hypoxic-inducible factor-1 (HIF-1), composed of 
and 
submits, 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, is not only activated by hypoxia but also
by peptides such as interleukin-1 (IL-1) in normoxia. In
this paper, we demonstrated that exposure of normal human
cytotrophoblast cells to IL-1 stimulated the
expression of HIF-1 protein. Meanwhile,
IL-1 also induced the secretion of VEGF in normal
human cytotrophoblast cells. Our data indicated that
IL-1 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 protein expression and
VEGF secretion by IL-1. These data indicate that in
normal human cytotrophoblast cells, IL-1 induces
HIF-1-mediated VEGF secretion, and that
IL-1-stimulated- ERK1/2 activation may be involved
in this process.
Key words:
Pregnancy •
Cytokines •
Growth factors •
Signal transduction •
Trophoblast
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