Hypoxia andP. gingivalisSynergistically Induce HIF-1 and NF-κB Activation in PDL Cells and Periodontal Diseases

Abstract

Periodontitis is characterized by deep periodontal pockets favoring the proliferation of anaerobic bacteria likePorphyromonas gingivalis(P. gingivalis), a periodontal pathogen frequently observed in patients suffering from periodontal inflammation. Therefore, the aim of the present study was to investigate the signaling pathways activated by lipopolysaccharide (LPS) ofP. gingivalis(LPS-PG) and hypoxia in periodontal ligament (PDL) cells. The relevant transcription factors nuclear factor-kappa B (NF-κB) and hypoxia inducible factor-1 (HIF-1) were determined. In addition, we analyzed the expression of interleukin- (IL-) 1β, matrix metalloproteinase-1 (MMP-1), and vascular endothelial growth factor (VEGF) in PDL cells on mRNA and protein level. This was accomplished by immunohistochemistry of healthy and inflamed periodontal tissues. We detected time-dependent additive effects of LPS-PG and hypoxia on NF-κB and HIF-1αactivation in PDL cells followed by an upregulation of IL-1β, MMP-1, and VEGF expression. Immunohistochemistry performed on tissue samples of gingivitis and periodontitis displayed an increase of NF-κB, HIF-1, and VEGF immunoreactivity in accordance with disease progression validating the importance of thein vitroresults. To conclude, the present study underlines the significance of NF-κB and HIF-1αand their target genes VEGF, IL-1β, and MMP-1 inP. gingivalisand hypoxia induced periodontal inflammatory processes.