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| Author(s): |
Carlos Eduardo Palanch Repeke
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Bauru. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Odontologia de Bauru (FOB/SDB) |
| Defense date: | 2009-03-23 |
| Examining board members: |
Gustavo Pompermaier Garlet;
Ana Paula Campanelli;
Paula Cristina Trevilatto
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| Advisor: | Gustavo Pompermaier Garlet |
| Abstract | |
Periodontal disease (PD) development is highly influenced by the host immune response to the bacterial challenge. Despite the protective role of this response against infectious agents it leads to periodontal tissues destruction. In this study, we analyzed the role of chemokine MIP-1 on the immunomodulation of experimental PD in mice. C57Bl/6 (WT) mice infected with A. actinomycetemcomitans developed an intense inflammatory reaction and severe alveolar bone resorption, associated with a high expression of MIP-1 and the migration of CCR5+ and CCR1+ cells to the periodontal tissues. In addition, an intense expression of Th1 (IFN-) and inflammatory (TNF-) cytokines, RANKL and MMPs are associated with the disease progression. However, mice genetically deficient of MIP-1 (MIP-1KO), when infected with A. actinomycetemcomitans, developed a very similar response pattern to that observed for WT strain. Indeed, the absence of MIP-1 does not interfere in inflammatory cells migration to periodontal tissues and alveolar bone resorption in response to A. actinomycetemcomitans infection. Similarly, the expression of cytokines (TNF-, IFN- and IL-10), osteoclastogenic factors (RANKL and OPG) and MMPs and its inhibitors (MMP-1, MMP-2, MMP-3, TIMP-1 and TIMP-3) was similar between WT and MIP-1KO strains. Furthermore, the lack of MIP-1 does not interfere in the control of A. actinomycetemcomitans infection as demonstrated by the similar bacterial load, and similar levels of the antimicrobial MPO and iNOS. Such results can be explained by the relative redundancy of chemokine system, where more than one chemokine can bind to the same receptor. Indeed, chemokines, such as MIP-1 and RANTES, which use the same receptors used by MIP-1 (CCR1 and CCR5), are intensely expressed in periodontal tissues of mice infected with A. actinomycetemcomitans, regardless of the absence of MIP-1. In accordance, the treatment of mice with Met-RANTES, a specific antagonist of the receptors CCR5 and CCR1, resulted in a significant reduction in the influx of inflammatory cells and alveolar bone loss when compared with untreated mice. Our results demonstrate that the absence of MIP-1 does not affect the development of experimental periodontitis in mice, probably due to the presence of homologous chemokines that overcome the absence of this chemokine. (AU) | |
| FAPESP's process: | 07/01705-7 - The role of MIP-1alpha on the immunomodulation of experimental periodontal disease |
| Grantee: | Carlos Eduardo Palanch Repeke |
| Support Opportunities: | Scholarships in Brazil - Master |