LPS from Porphyromonas gingivalis Induces Functional Kinin B₁ Receptor Upregulation

It has been clearly demonstrated that kinin B1 receptors are highly upregulated under several stressful conditions, such as infection. In spite of that, there is no evidence indicating whether periodontal pathogens might modulate the inflammatory responses mediated by kinin B1 receptor activation.

Objectives: To evaluate the effects of local treatment with LPS from Porphyromonas gingivalis (Pg-LPS)on edema formation induced by B1 receptor agonist stimulation and to pharmacologically determine some of the mechanisms underlying Pg-LPS-induced B1 receptor up-regulation.

Methods: We have employed an in vivo approach in which Pg-LPS (3µg) was injected locally into the rat paw (n=6/group). Following several time intervals of Pg-LPS treatment (3-72h), the edema was induced by the intraplantar injection of the selective B1 receptor agonist des-Arg9-BK (100nmol/paw) and measured by means of a plethysmometer.

Results: Injection of des-Arg9-BK induced a slight edema in naïve rats. Conversely, this agonist evoked a marked edema in animals that had been locally pre-treated with Pg-LPS. The upregulation of B1 receptor-mediated edema peaked at 24h after Pg-LPS administration (55 % of increase). Interestingly, Pg-LPS-induced functional B1 receptor upregulation was significantly diminished by pre-treating animals with the glucocorticoid dexamethasone (0.5mg/kg, s.c., 2h before Pg-LPS), the monoclonal chimeric anti-TNFa antibody Infliximab (1mg/kg, s.c., 15min before) and the pro-resolution mediator Resolvin E1 (300ng/animal, i.p., 30min prior to Pg-LPS). The observed percentages of inhibition were: 47%, 33% and 59%, respectively.

Conclusions: Present data clearly show that kinin B1 receptors are functionally up-regulated by Pg-LPS, in a multi-mediated process. These findings indicate that B1 receptor modulation represents a relevant pathway for the inflammatory responses evoked by Porphyromonas gingivalis and its virulence factors.

Support: CNPq (473012/2006-5; Brazil).