Actinobacillus actinomycetemcomitans-induced periodontal disease in mice: patterns of cytokine, chemokine, and chemokine receptor expression and leukocyte migration

Autor(es)

Garlet, Gustavo P. ^[1] ; Avila-Campos, Mario J. ; Milanezi, Cristiane M. ; Fereira, Beatriz R. ; Silva, João S.

Afiliação do(s) autor(es)

^[1] Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto. Departamento de Bioquímica e Imunologia - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Microbes and Infection; v. 7, n. 4, p. 738-747, Apr. 2004.
• Área do conhecimento: Ciências da Saúde - Odontologia
• Assunto(s): Periodontia Patologia bucal

Resumo

Although the pathogenesis of periodontal disease (PD) is not well known, cytokines, chemotactic factors and inflammatory cells are certainly involved in the disease outcome. Here, we characterized the evolution of the PD induced by Actinobacillus actinomycetemcomitans in mice, showing that oral inoculation of these bacteria leads to the migration of leukocytes to periodontal tissues and marked alveolar bone resorption. We found the expression of pro-inflammatory and Th1-type cytokines including TNF-a, IFN-? and IL-12 in periodontal tissues after infection with A. actinomycetemcomitans, from the early stages after infection and throughout the course of the disease. Similar kinetics of expression were found for the chemokines CCL5, CCL4, CCL3 and CXCL10 and for the receptors CCR5 and CXCR3, all of them linked to the Th1-type pattern. The expression of the Th2-type mediators IL-10, CCL1 and their receptors CCR4 and CCR8 was detected only after 30 days of infection, determining a time-dependent mixed pattern of polarized immune response. The chemokine expression was correlated with the presence of polymorphonuclear leukocytes, macrophages, CD4 and CD8 lymphocytes, and B cells in the inflammatory infiltrate. Interestingly, during the predominance of the Th1-type response, a sharp increase in the number of inflammatory cells and intense bone loss was seen. By contrast, after the increased expression of Th2-type mediators, the number of inflammatory cells remained constant. Our data demonstrate that mice subjected to oral inoculation of A. actinomycetemcomitans represent a useful model for the study of PD. In addition, our results suggest that expression of cytokines and chemokines can drive the selective recruitment of leukocyte subsets to periodontal tissues, which could determine the stable or progressive nature of the lesion. (AU)

• Processo FAPESP: 04/06731-8 - Modulacao da resposta imune em doencas periodontais induzidas experimentalmente
• Beneficiário: João Santana da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 01/09998-7 - Estudo do papel do IFN-gamma, TNF-algha, IL-4 e iNOS na imunomodulação da doença periodontal
• Beneficiário: Gustavo Pompermaier Garlet
• Modalidade de apoio: Bolsas no Brasil - Doutorado