title: Inactivation of tissue inhibitor of metalloproteinases-1 (TIMP-1) by Porphyromonas gingivalis.
abstract: In response to periodontal inflammation, host cells release matrix metalloproteinases (MMPs) that contribute to periodontal tissue breakdown unless the tissue inhibitors of metalloproteinases (TIMPs) neutralize their activity. In this study, the capacity of Porphyromonas gingivalis to inactivate TIMP-1 was investigated. Proteolytic digestion of TIMP-1 was monitored by SDS-PAGE and Western immunoblotting. Planktonic cells and biofilms of P. gingivalis degraded TIMP-1 with production of several lower molecular mass fragments. Incorporation of human serum in the assay mixture had no effect on the degradation of TIMP-1 by P. gingivalis, whereas a cysteine proteinase inhibitor caused a complete inhibition. Using a fluorogenic assay, it was found that TIMP-1 treated with P. gingivalis lost its capacity to inhibit MMP-9 activity. This study revealed the potential of P. gingivalis to inactivate TIMP-1 through proteolytic degradation. This phenomenon may contribute to increasing significantly the level of active MMPs in affected periodontal sites and subsequently favor tissue destruction.
authors.affiliation: Groupe de Recherche en Ecologie Buccale, Faculté de Médecine Dentaire, Université Laval, Québec, QC, Canada G1K 7P4. daniel.grenier@greb.ulaval.ca
authors.forename: D
authors.initials: D
authors.lastname: Grenier
authors.forename: D
authors.initials: D
authors.lastname: Mayrand
mesh_terms: D003470:Culture Media; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D016966:Porphyromonas gingivalis / Q000254:growth & development / Q000378:metabolism*; D011480:Protease Inhibitors / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*
chemical_list: D003470:Culture Media; D011480:Protease Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1