Efeito modulatório de fatores de virulência de Porphyromonas gingivalis sobre os receptores B1 para as cininas na pata de rato

• Ano de defesa: 2009
• Autor(a) principal: Dornelles, Fabiana Noronha
• Orientador(a): Campos, Maria Martha
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Pontifícia Universidade Católica do Rio Grande do Sul; Porto Alegre
• Palavras-chave em Português: BIOLOGIA CELULAR; VÍRUS; DOENÇAS PERIODONTAIS; EXPERIMENTAÇÃO ANIMAL; INFLAMAÇÃO
• Link de acesso: http://hdl.handle.net/10923/1290

It has been demonstrated that kinin B1 receptors are highly upregulated under several stressful stimuli, such as infection. In spite of that, there is no evidence indicating whether Porphyromonas gingivalis LPS (Pg-LPS), a preferential TLR2 activator, might lead to B1 receptor upregulation. In this study, we demonstrate that Pg-LPS injection into the rat paw resulted in a marked functional upregulation of B1 receptors (as measured by an increase of B1 receptor-induced edema formation), which was preceded by a rapid raise in B1 receptor mRNA expression. The local administration of Pg-LPS also resulted in a prominent production of the proinflammatory cytokine TNF-G, followed by an increase of neutrophil influx; both events were observed at time periods prior to B1 receptor induction. The functional and molecular Pg-LPS-elicited B1 receptor upregulation was significantly reduced by the glucocorticoid dexamethasone, and to a lesser extent by the chimeric anti-TNFa antibody infliximab. Of high relevance, we show for the first time that a single administration of the pro-resolution lipid mediator Resolvin E1 was able to markedly down-regulate Pg-LPS-driven B1 receptor expression, probably by inhibiting TNFG production and neutrophil migration to the inflammatory set. Collectively, the present findings clearly suggest that TLR2 activation by Pg-LPS is able to induce the upregulation of B1 receptors, through mechanisms involving TNFa release and neutrophil influx, which are largely sensitive to Resolvin E1. It is tempting to suggest that kinin B1 receptors might well represent a pivotal pathway for the inflammatory responses evoked by P. gingivalis and its virulence factors.