title: Periodontal treatment downregulates protease-activated receptor 2 in human gingival crevicular fluid cells.
abstract: Protease-activated receptor 2 (PAR2) is implicated in the pathogenesis of chronic inflammatory diseases, including periodontitis; it can be activated by gingipain and produced by Porphyromonas gingivalis and by neutrophil protease 3 (P3). PAR2 activation plays a relevant role in inflammatory processes by inducing the release of important inflammatory mediators associated with periodontal breakdown. The effects of periodontal treatment on PAR2 expression and its association with levels of proinflammatory mediators and activating proteases were investigated in chronic periodontitis patients. Positive staining for PAR2 was observed in gingival crevicular fluid cells and was reflective of tissue destruction. Overexpression of PAR2 was positively associated with inflammatory clinical parameters and with the levels of interleukin-6 (IL-6), IL-8, tumor necrosis factor alpha, matrix metalloprotease 2 (MMP-2), MMP-8, hepatocyte growth factor, and vascular endothelial growth factor. Elevated levels of gingipain and P3 and decreased levels of dentilisin and the protease inhibitors secretory leukocyte protease inhibitor and elafin were also associated with PAR2 overexpression. Healthy periodontal sites from individuals with chronic periodontitis showed diminished expression of PAR2 mRNA and the PAR2 protein (P < 0.05). Furthermore, periodontal treatment resulted in decreased PAR2 expression and correlated with decreased expression of inflammatory mediators and activating proteases. We concluded that periodontal treatment resulted in decreased levels of proteases and that proinflammatory mediators are associated with decreased PAR2 expression, suggesting that PAR2 expression is influenced by the presence of periodontal infection and is not a constitutive characteristic favoring periodontal inflammation.
authors.affiliation: Division of Periodontics, Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Vanessa Tubero
authors.initials: VT
authors.lastname: Euzebio Alves
authors.forename: Henrique Aparecido
authors.initials: HA
authors.lastname: Bueno da Silva
authors.forename: Bruno Nunes
authors.initials: BN
authors.lastname: de França
authors.forename: Rosangela Santos
authors.initials: RS
authors.lastname: Eichler
authors.forename: Luciana
authors.initials: L
authors.lastname: Saraiva
authors.forename: Maria Helena Catelli
authors.initials: MH
authors.lastname: de Carvalho
authors.forename: Marinella
authors.initials: M
authors.lastname: Holzhausen
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism; D000328:Adult; D001426:Bacterial Proteins; D002918:Chymotrypsin / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D053492:Elafin / Q000378:metabolism; D005260:Female; D000080867:Gingipain Cysteine Endopeptidases; D005883:Gingival Crevicular Fluid / Q000166:cytology*; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D008875:Middle Aged; D053146:Myeloblastin / Q000378:metabolism; D010447:Peptide Hydrolases; D010514:Periodontal Pocket / Q000276:immunology; D010518:Periodontitis / Q000276:immunology / Q000378:metabolism* / Q000628:therapy*; D016966:Porphyromonas gingivalis / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D044464:Receptor, PAR-2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D053492:Elafin; D000080867:Gingipain Cysteine Endopeptidases; C066855:HGF protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; C506806:PI3 protein, human; D012333:RNA, Messenger; D044464:Receptor, PAR-2; D053481:Secretory Leukocyte Peptidase Inhibitor; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor; D010447:Peptide Hydrolases; C102570:dentilisin; D002918:Chymotrypsin; D053146:Myeloblastin; D003546:Cysteine Endopeptidases; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8
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