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| Author(s): |
Vanessa Tubero Euzébio Alves
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Odontologia (FO/SDO) |
| Defense date: | 2014-06-09 |
| Examining board members: |
Marinella Holzhausen Caldeira;
Maria Helena Catelli de Carvalho;
Joni Augusto Cirelli;
Ibrahim Alpdogan Kantarci;
Marcelo Nicolas Muscara
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| Advisor: | Marinella Holzhausen Caldeira |
| Abstract | |
Protease-activated receptor-2 (PAR2) is implicated in the pathogenesis of chronic inflammatory diseases including periodontitis; it can be activated by gingipain, produced by Porphyromonas gingivalis (P. 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. In the present study, the effect of non-surgical periodontal treatment on PAR2 expression and its association with levels of pro-inflammatory mediators, and activating proteases were investigated in chronic periodontitis patients. Moreover it was evaluated in vitro the role of MAPK-p38 signaling pathway during PAR2 activation and its influence on superoxide production and phagocytosis capacity in peripheral human neutrophils infected with P. gingivalis. A significant mRNA and protein over-expression of PAR2 (P < 0.05) in gingival crevicular fluid cells was positively associated to inflammatory clinical parameters, and to the levels of interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, matrix metalloproteases (MMP)-2, MMP-8, hepatocyte growth factor, and vascular endothelial growth factor (evaluated by Bioplex). Elevated levels of gingipain and P3 (P < 0.05), and decreased levels of dentilisin mRNA, and protease inhibitors, secretory leucocyte protease inhibitor and elafina (P < 0.05) (evaluated by ELISA), were also associated to PAR2 overexpression. Periodontally healthy sites from chronic periodontitis individuals showed a diminished expression of PAR2 mRNA and PAR2 protein level (P < 0.05). Furthermore, periodontal treatment resulted in decreased PAR2 expression (P < 0.05), correlated with decreased expression of inflammatory mediators (P < 0.05) and activating proteases (P < 0.05). Moreover, PAR2 antagonist reduced significantly superoxide production in human neutrophils (P < 0.05) showing the role of PAR2 on this important cellular function. We concluded that periodontal treatment resulted on decreased levels of proteases, and pro-inflammatory mediators is associated to decreased PAR2 expression, therefore suggesting that PAR2 expression is influenced by the presence of periodontal infection, and not a constitutive characteristic favoring periodontal inflammation. (AU) | |
| FAPESP's process: | 10/20477-8 - Evaluation of the protease activated receptor 2(PAR-2) expression in chronic periodontitis patients, before and after non-surgical periodontal treatment |
| Grantee: | Vanessa Tubero Euzebio Alves |
| Support Opportunities: | Scholarships in Brazil - Doctorate |