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The role of NOD1 and NOD2 in autophagic mechanisms of macrophages and osteoclasts infected with Porphyromonas gingivalis

Grant number: 14/11958-3
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Start date: January 01, 2015
End date: August 31, 2016
Field of knowledge:Health Sciences - Dentistry - Periodontology
Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Sandra Yasuyo Fukada Alves
Grantee:Erivan Schnaider Ramos Junior
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Periodontitis is a multifactorial infectious and inflammatory chronic disease that constitutes a great challenge for researchers. One of the factors of disease severity / progression is an intense immune / inflammatory response which can lead to bone resorption triggered by the host cells in response to the complexity of bacteria and their products. Amongst these bacteria, Porphyromonas gingivalis has been a major causative agent of dysbiosis in the oral microbiota leading to disease progression. The host-pathogen interaction opens up new and interesting possibilities in the study of the immune and osseous system. In this context, the discovery of intracellular receptors (Nod1 and Nod2) which can recognize pathogens associated molecular patterns and induce an immune response has been associated with the knowledge that P. gingivalis is able to interact with such receptors, opening a new field to study. It has been demonstrated the involvement of autophagy, a new arsenal component of the innate immune system, in the production's modulation of pro-inflammatory cytokines in cells from Nod1 and Nod2 deficient mice. However, the role of these receptors in autophagic cells involved in mechanisms of bone resorption, such as macrophages and osteoclasts in the context of P. gingivalis infection remains unclear. Thus, the aim of this study is to characterize the role of autophagy caused by P. gingivalis in modulating the secretion of inflammatory mediators, cell death, damage / mitochondrial activity , ROS generation and lysosome traffic using bone marrow derived macrophages and osteoclasts ( in vitro ) of Nod1 and Nod2-deficient mice.Expected contribution to the field: provide technical / scientific information for assessing the possibility of using such information for modulating the immune response, specifically the Nod1 and Nod2 receptors, in order to give a possible clinical application as well as possibility of clinical application reaching the so-called "Translational Periodontology". It is important to emphasize that this study consists of a line of research approved by FAPESP being consistent with the work currently in development by the research group. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RAMOS-JUNIOR, ERIVAN S.; LEITE, GISELE A.; CARMO-SILVA, CECILIA C.; TAIRA, THAISE M.; NEVES, KARLA B.; COLON, DAVID F.; DA SILVA, LEA A. B.; SALVADOR, SERGIO L.; TOSTES, RITA C.; CUNHA, FERNANDO Q.; et al. Adipokine Chemerin Bridges Metabolic Dyslipidemia and Alveolar Bone Loss in Mice. Journal of Bone and Mineral Research, v. 32, n. 5, p. 974-984, . (15/09034-0, 13/08216-2, 12/50842-5, 14/11958-3)
DA CUNHA, MARCOS GUILHERME; RAMOS-JUNIOR, ERIVAN SCHNAIDER; FRANCHIN, MARCELO; TAIRA, THAISE MAYUMI; BEUTLER, JOHN A.; NOBRE FRANCO, GILSON CESAR; IKEGAKI, MASAHARU; DE ALENCAR, SEVERINO MATIAS; FUKADA, SANDRA YASUYO; ROSALEN, PEDRO LUIZ. Effects of Cinnamoyloxy-mammeisin from Geopropolis on Osteoclast Differentiation and Porphyromonas gingivalis-Induced Periodontitis. Journal of Natural Products, v. 80, n. 6, p. 1893-1899, . (12/22002-2, 11/23635-6, 14/11958-3)