Regulation of NF-kappa B and cell death by bacterial gingipains

The role of non-caspase proteases in the regulation of programmed cell death is relatively under-studied. In this short communication, we report that infection of human gingival fibroblast (HGF) cells ex vivo by Porphyromonas gingivalis rapidly activated NF-kappa B, an antiapoptotic player; PI3 kinase was also induced, and together, they inhibited apoptosis. Later, pro-apoptotic cellular genes, including caspases, were induced. Apoptosis was evidenced by the degradation of nuclear DNA and activation of caspases. Unexpectedly, a P. gingivalis mutant that lacked all three major gingipain proteases was defective in promoting apoptosis, which was consistent with the cleavage of procaspase-3 to the active form by the culture supernatant of wild type P. gingivalis, but not that of the triple protease mutant. These results suggest that cellular death in the P. gingivalis-infected gum may be orchestrated by gingipain-regulated apoptotic factors.