Abstract
Growing evidence indicates that inflammation is a contributing factor leading to cancer development. However, pathways involved in this progression are not well understood. The involvement of DEC1 in cancer prompted us to examine whether pro-inflammatory cytokine interleukin-1β (IL-1β) induces the expression of DEC1 in oral inflammation. We found that IL-1β up-regulated DEC1 and hypoxia-inducible factor-1α (HIF-1α) protein and elevated the HIF-1α-responsive gene vascular endothelial growth factor (VEGF) expression in human primary gingival cells. HIF-1α and DEC1 immunoreactivity were significantly higher in the cases of gingival inflammation. We demonstrate that IL-1β up-regulates DEC1 and HIF-1α protein through a classical inflammatory signaling pathway involving Akt. Our data strongly suggest that PI-3K-Akt is an upstream participant in IL-1β-mediated DEC1 and HIF-1α induction. This is supported by the following data: (1) IL-1β induces 473 serine phosphorylation of Akt; (2) IL-1β-mediated Akt activation occurs in a PI-3K-dependent manner, and specific inhibition of PI-3K prevents Akt phosphorylation; and (3) inhibition of Akt prevents IL-1β-mediated DEC1 and HIF-1α induction. Taken together, these results suggest that DEC1 is one of the important transcription factors in inflammation.
Copyright © 2012 Wiley Periodicals, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bacteroidaceae Infections / metabolism
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Bacteroidaceae Infections / pathology
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Blotting, Western
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Cells, Cultured
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Chromones / pharmacology
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Epithelial Cells / drug effects
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Epithelial Cells / metabolism
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Fibroblasts / drug effects
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Fibroblasts / metabolism
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Gingiva / cytology
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Gingiva / metabolism
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Gingiva / pathology*
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Immunohistochemistry
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Inflammation / metabolism
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Inflammation / pathology
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Interleukin-1beta / pharmacology*
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Male
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Morpholines / pharmacology
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphorylation
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Porphyromonas gingivalis / pathogenicity
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism*
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Rats
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Rats, Sprague-Dawley
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Recombinant Proteins / pharmacology
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Serine / metabolism
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Signal Transduction
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
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Up-Regulation
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism
Substances
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Chromones
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DELEC1 protein, human
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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IL1B protein, human
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Interleukin-1beta
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LY 290042
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Morpholines
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Recombinant Proteins
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Tumor Suppressor Proteins
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Vascular Endothelial Growth Factor A
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Serine
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Proto-Oncogene Proteins c-akt