Gene interactions and pathways from curated databases and text-mining
Biol Reprod 2004, PMID: 14960485

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.

Qian, Dong; Lin, Hai-Yan; Wang, Hong-Mei; Zhang, Xuan; Liu, Dong-Lin; Li, Qing-Lei; Zhu, Cheng

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.

Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System
Document information provided by NCBI PubMed

Text Mining Data

VEGF → IL-1: " Meanwhile, IL-1 beta also induced the secretion of VEGF in normal human cytotrophoblast cells "

VEGF → IL-1 beta: " Meanwhile, IL-1 beta also induced the secretion of VEGF in normal human cytotrophoblast cells "

VEGF → HIF- 1 alpha: " 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 "

VEGF → IL-1: " 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 "

VEGF → 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 "

ERK1/2 → 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 "

IL-1 → ERK1/2: " 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 "

IL-1 → 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 "

VEGF — ERK1/2: " 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 "

Manually curated Databases

No curated data.