Expression of Hypoxia-Inducible Factor-1 alpha in Human Periodontal Tissue

Background: Hypoxia-inducible factor (HIF)-1 is a key transcription factor responding to hypoxia. It is composed of an oxygen-sensitive a subunit (HIF-1 alpha) and a constitutively expressed 13 subunit. Increasing evidence indicates an essential role for HIF-1 alpha in infection and immunity. Because inflamed periodontium is thought to be hypoxic, we hypothesize that HIF-1 alpha is expressed and related to its upstream regulator tumor necrosis factor (TNF)-alpha and downstream effecter vascular endothelial growth factor (VEGF). Methods: Human gingival biopsies were collected from advanced periodontitis sites and clinically healthy sites, and immunohistochemically examined for HIF-1 alpha and VEGF peptides. The messenger ribonucleic acid (mRNA) and protein levels of HIF-1 alpha, VEGF, and TNF-alpha in the biopsies were then assessed by reverse transcription polymerase chain reaction and Western blotting. Results: HIF-1 alpha positive immunoreactivity was detected in the nuclei of epithelial and endothelial cells. In periodontal pockets, there was a marked increase in the proportion of fibroblast-like cells and leukocyte-like cells expressing HIF-1 alpha. Protein levels of HIF-1 alpha, VEGF, and TNF-alpha were significantly higher in periodontal pockets than in control gingival samples. The mRNA expression of VEGF and TNF-alpha was also increased in periodontal pockets. Conclusion: HIF-1 alpha is expressed in healthy and diseased periodontium and may be related to TNF-alpha and VEGF function during periodontitis. J Periodontol 2011;82:136-141.