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 proteinases produced by the oral anaerobic bacterium Porphyromonas gingivalis, which has been shown to act as major pathogen in the development and progression of periodontal diseases. These enzymes are also important for this organism 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 P. gingivalis. Fibroblasts incubated with the culture supernatant of P. gingivalis showed a time-dependent loss of the adhesion 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 treatment. The detached cells became committed to death by disruption of contacts between adhesion molecules. In contrast, the culture supernatants from the Rgp-deficient mutants produced no significant changes in either cell adhesion or viability. Prior treatment of the culture supernatant of P. gingivalis with an Rgp inhibitor, but not a Kgp inhibitor, strongly inhibited the detachment of fibroblasts followed by cell death. These results suggest that Rgp disrupts the integrin-fibronectin interactions in fibroblasts, thereby contributing to the damage of periodontal tissues in periodontal diseases caused by P. gingivalis.