IL-1β-mediated up-regulation of DEC1 in human gingiva cells via the Akt pathway.
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.
Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo, Matsudo, Japan. bhawal.ujjal.kumar@nihon-u.ac.jp
Ujjal K
UK
Bhawal
Yumi
Y
Ito
Keiji
K
Tanimoto
Fuyuki
F
Sato
Katsumi
K
Fujimoto
Takeshi
T
Kawamoto
Tomonori
T
Sasahira
Nobushiro
N
Hamada
Hiroki
H
Kuniyasu
Hirohisa
H
Arakawa
Yukio
Y
Kato
Yoshimitsu
Y
Abiko
D000818:Animals; D016866:Bacteroidaceae Infections / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D016966:Porphyromonas gingivalis / Q000472:pathogenicity; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D002867:Chromones; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D053583:Interleukin-1beta; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins; D012694:Serine; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; C403671:DELEC1 protein, human; C497442:HIF1A protein, human; C508585:IL1B protein, human; C549075:LY 290042