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-1 beta (IL-1 beta) induces the expression of DEC1 in oral inflammation. We found that IL-1 beta up-regulated DEC1 and hypoxia-inducible factor-1a (HIF-1a) protein and elevated the HIF-1a-responsive gene vascular endothelial growth factor (VEGF) expression in human primary gingival cells. HIF-1a and DEC1 immunoreactivity were significantly higher in the cases of gingival inflammation. We demonstrate that IL-1 beta up-regulates DEC1 and HIF-1a protein through a classical inflammatory signaling pathway involving Akt. Our data strongly suggest that PI-3KAkt is an upstream participant in IL-1 beta-mediated DEC1 and HIF-1a induction. This is supported by the following data: (1) IL-1 beta induces 473 serine phosphorylation of Akt; (2) IL-1 beta-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-1 beta-mediated DEC1 and HIF-1a induction. Taken together, these results suggest that DEC1 is one of the important transcription factors in inflammation. J. Cell. Biochem. 113: 32463253, 2012. (c) 2012 Wiley Periodicals, Inc.