Your browser doesn't support javascript.
loading
Porphyromonas gingivalis-derived RgpA-Kgp Complex Activates the Macrophage Urokinase Plasminogen Activator System: IMPLICATIONS FOR PERIODONTITIS.
Fleetwood, Andrew J; O'Brien-Simpson, Neil M; Veith, Paul D; Lam, Roselind S; Achuthan, Adrian; Cook, Andrew D; Singleton, William; Lund, Ida K; Reynolds, Eric C; Hamilton, John A.
Afiliação
  • Fleetwood AJ; From the Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia, andrew.fleetwood@unimelb.edu.au.
  • O'Brien-Simpson NM; the Oral Health Cooperative Research Centre, Melbourne Dental School, University of Melbourne, Victoria 3010, Australia, and.
  • Veith PD; the Oral Health Cooperative Research Centre, Melbourne Dental School, University of Melbourne, Victoria 3010, Australia, and.
  • Lam RS; the Oral Health Cooperative Research Centre, Melbourne Dental School, University of Melbourne, Victoria 3010, Australia, and.
  • Achuthan A; From the Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
  • Cook AD; From the Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
  • Singleton W; the Oral Health Cooperative Research Centre, Melbourne Dental School, University of Melbourne, Victoria 3010, Australia, and.
  • Lund IK; the Finsen Laboratory, Rigshospitalet and the Biotech Research and Innovation Centre, Copenhagen University, 1165 Copenhagen, Denmark.
  • Reynolds EC; the Oral Health Cooperative Research Centre, Melbourne Dental School, University of Melbourne, Victoria 3010, Australia, and.
  • Hamilton JA; From the Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
J Biol Chem ; 290(26): 16031-42, 2015 Jun 26.
Article em En | MEDLINE | ID: mdl-25979345
Urokinase plasminogen activator (uPA) converts plasminogen to plasmin, resulting in a proteolytic cascade that has been implicated in tissue destruction during inflammation. Periodontitis is a highly prevalent chronic inflammatory disease characterized by destruction of the tissue and bone that support the teeth. We demonstrate that stimulation of macrophages with the arginine- and lysine-specific cysteine protease complex (RgpA-Kgp complex), produced by the keystone pathogen Porphyromonas gingivalis, dramatically increased their ability to degrade matrix in a uPA-dependent manner. We show that the RgpA-Kgp complex cleaves the inactive zymogens, pro-uPA (at consensus sites Lys(158)-Ile(159) and Lys(135)-Lys(136)) and plasminogen, yielding active uPA and plasmin, respectively. These findings are consistent with activation of the uPA proteolytic cascade by P. gingivalis being required for the pathogen to induce alveolar bone loss in a model of periodontitis and reveal a new host-pathogen interaction in which P. gingivalis activates a critical host proteolytic pathway to promote tissue destruction and pathogen virulence.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Periodontite / Cisteína Endopeptidases / Ativador de Plasminogênio Tipo Uroquinase / Porphyromonas gingivalis / Adesinas Bacterianas / Macrófagos Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Periodontite / Cisteína Endopeptidases / Ativador de Plasminogênio Tipo Uroquinase / Porphyromonas gingivalis / Adesinas Bacterianas / Macrófagos Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article