Arg-gingipain is responsible for the degradation of cell adhesion molecules of human gingival fibroblasts and their death induced by Porphyromonas gingivalis

Arg-gingipain (Rgp) and Lys-gingipain (Kgp) are two major cysteine proteina ses produced by the oral anaerobic bacterium Porphyromonas gingivalis, whic h has been shown to act as major pathogen in the development and progressio n of periodontal diseases. These enzymes are also important for this organi sm to proliferate and survive in periodontal pockets. Here we show that Rgp is responsible for the disruption of fibronectin-integrin interactions in human gingival fibroblasts by Fl gingivalis. Fibroblasts incubated with the culture supernatant of P. gingivalis showed a time-dependent loss of the a dhesion activity. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting revealed that fibronectin and integrin subunits alpha2, beta1 and beta3 in the fibroblast culture largely disappeared with the tre atment. The detached cells became committed to death by disruption of conta cts between adhesion molecules. In contrast, the culture supernatants from the Rgp-deficient mutants produced no significant changes in either cell ad hesion or viability. Prior treatment of the culture supernatant of Fl gingi valis with an Rgp inhibitor, but not a Kgp inhibitor, strongly inhibited th e detachment of fibroblasts followed by cell death. These results suggest t hat Rgp disrupts the integrin-fibronectin interactions in fibroblasts, ther eby contributing to the damage of periodontal tissues in periodontal diseas es caused by Fl gingivalis.