Porphyromonas gingivalis degrades integrin β1 and induces AIF-mediated apoptosis of epithelial cells.

Background:Porphyromonas gingivalis, a major pathogen of chronic periodontitis, adheres to and invades epithelial cells via an interaction between fimbriae and integrin. P. gingivalis proliferation and infection may affect the survival of cells. In this study, we further examined alternative signaling pathways mediating epithelial-cell death induced by P. gingivalis and the role of the cell-adhesion molecule integrin. Methods: Human epithelial KB cells interacted with P. gingivalis to evaluate cell death by Annexin V-propidium iodide (PI) staining. JC-1 staining was used to measure mitochondrial membrane potential (MMP). The mRNA and protein of integrin β1, apoptosis-inducing factor (AIF) and caspase-3 were detected by real-time PCR and western blot. Caspase-3 activity was analyzed by spectrophotometry. Results:P. gingivalis infection downregulated integrin β1 and led to cell detachment in a dose and time-dependent manner. Large amount of P. gingivalis induced MMP depolarization and apoptosis in KB cells. Moreover, P. gingivalis up-regulated AIF, but not activate caspase-3 during apoptosis. In addition, AIF inhibitor N-Phenylmaleimide almost inhibited the P. gingivalis-induced apoptosis. Conclusions:P. gingivalis disrupts epithelial-cell adhesion by degrading integrin β1 and induces caspase-independent, AIF-mediated mitochondrial apoptosis, which may promote the damage of oral tissue.