| Grant number: | 10/05632-7 |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| Start date: | June 01, 2010 |
| End date: | March 31, 2013 |
| Field of knowledge: | Health Sciences - Dentistry - Periodontology |
| Principal Investigator: | Carlos Rossa Junior |
| Grantee: | João Antonio Chaves de Souza |
| Host Institution: | Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil |
Abstract Recognition of pathogenic bacteria by the host is initially mediated by the innate immune response through detection of pathogen-associated molecular patterns (PAMPs) by Toll-like receptors (TLR) and Nucleotide-oligomerization domain (Nod) proteins. Since the oral cavity, as well as other mucosal surfaces, is continuously colonized with non-pathogenic bacteria that also present PAMPs, there has to be an endogenous negative regulatory mechanism in place to prevent an overt host response with deleterious consequences. Specifically in the oral mucosa, it is not clear how the immune system is able to quickly distinguish between commensal and pathogenic bacteria and tailor the host response. Nod proteins were initially described as 'intracellular TLRs' that recognize PAMPs associated with bacteria invading the cytosol; however these proteins have been shown to modulate the activation of various signaling pathways involved in the expression of inflammatory genes, including p38 MAPK and NF-ºB in concert with TLR stimulation. We have found that Nod proteins are required for transcriptional activation of RANKL mediated by TLR signaling, suggesting a potential role of these proteins in inflammation and on the bone resorption associated with infectious conditions. However, there is paucity of information on the in vivo role of Nod proteins in the modulation of host-microbe interactions in the oral mucosa. Based on this information, our hypothesis is that Nod proteins play an important role in the modulation of the inflammatory reaction associated with periodontal diseases and its consequences, including alveolar bone resorption. To test this hypothesis, we propose the following specific aims:-Specific Aim #1: Assess the role of Nod proteins in the inflammation and bone resorption in experimentally-induced periodontal disease-Specific Aim #2: Describe the influence of Nod proteins on the cytokine and signaling networks associated with periodontal disease | |
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