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IL‐1β‐mediated up‐regulation of DEC1 in human gingiva cells via the Akt pathway
Author(s) -
Bhawal Ujjal K.,
Ito Yumi,
Tanimoto Keiji,
Sato Fuyuki,
Fujimoto Katsumi,
Kawamoto Takeshi,
Sasahira Tomonori,
Hamada Nobushiro,
Kuniyasu Hiroki,
Arakawa Hirohisa,
Kato Yukio,
Abiko Yoshimitsu
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24205
Subject(s) - protein kinase b , inflammation , phosphorylation , cancer research , microbiology and biotechnology , pi3k/akt/mtor pathway , transcription factor , cytokine , biology , chemistry , signal transduction , immunology , biochemistry , gene
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. J. Cell. Biochem. 113: 3246–3253, 2012. © 2012 Wiley Periodicals, Inc.