Proteolytic Activities of Oral Bacteria on ProMMP-9 and the Effect of Synthetic Proteinase Inhibitors

Abstract

Tissue reactions to bacteria lead to proinflammatory reactions involving matrix metalloproteinases (MMPs). Synthetic protease inhibitors may offer new possibilities to regulate bacterial proteases. We investigated proteolytic activities of certain periodontal bacteria, their effects on the latent proMMP-9, and the effects of synthetic MMP inhibitors and a serine protease inhibitor Pefabloc. The strains studied were Porphyromonas gingivalis, Prevotella intermedia, Peptostreptoccus micros, Prevotella nigrescens, Fusobacterium nucleatum, and 5 Aggregatibacter actinomycetemcomitans serotypes. Their gelatinolytic activities and the effects of certain synthetic MMP inhibitors and Pefabloc were analyzed by zymography. Bacterial effects on proMMP-9 conversion were investigated by Western immunoblot. All investigated periodontal bacteria produced gelatinolytic cell-bound and extracellular proteinases which could fragment latent proMMP-9, suggesting co-operative processing cascades in oral tissue remodeling. A. actinomycetemcomitans produced the weakest gelatinolytic activity. Synthetic proteinase inhibitors exhibited slight but clear reductive effects on the bacterial proteolytic activities. We conclude that targeted anti-proteolytic treatment modalities against bacterial-host proteolytic cascades can be developed.