Papel de mediadores inflamatórios na doença periodontal induzida por Aggregatibacter actinomycetemcomitans em camundongos

Abstract

Periodontal disease (PD) is a chronic inflammatory and alveolar bone destructive disease triggered by microorganisms as Aggregatibacter actinomycetemcomitans (Aa). Oral inoculation of mice with Aa or injections of its LPS (AaLPS) induce marked alveolar bone loss and local production of inflammatory mediators as clinical aggressive forms of PD in humans. Perhaps, signaling involved in recognition of AaLPS and the role of some mediators such as IL-12, MIF, lipidic mediators such as PAF and leukotrienes in alveolar bone resorption during PD is not well known. In the present study, experimental alveolar bone loss was inducedby AaLPS injections in wild-type (WT) mice and experimental PD was induced in WT or MIF (MIF-/-), PAFR (PAFR-/-) or 5-LO (5-LO-/-) knockout mice through oral inoculation of Aa. Our results show that the signaling through MyD88 is important to alveolar bone loss induced by AaLPS likely by activation of TNF- production. Oral inoculation of Aa induced significant neutrophil influx, production of inflammatory mediators and alveolar bone loss in WT mice. Perhaps, in the absence of MIF, PAFR or 5-LO, mice had reduced alveolar bone loss when compared to WT mice. In MIF-/- and 5-LO-/- mice this phenotype was associated with decreased neutrophil accumulation. WT mice as well as PAFR-/- mice submitted to oral inoculation of Aa presented neutrophil accumulation, increasedlevels of CXCL-1 and TNF- in periodontal tissues. In vitro, AaLPS enhanced osteoclastic activity in a MIF-dependent manner and the blockage of PAF and 5-LO impaired the resorption activity of AaLPS-activated osteoclasts. In conclusion, MIF and 5-LO has role in controlling bacterial growth in the context of PD contributing significantly to the progression of bone loss during PD by directly affecting differentiation and activity of osteoclasts and PAF directly affects osteoclasts activation without interferences in inflammatory response.