Abstract
Periodontitis is an infectious inflammatory disease of the supporting structures of the teeth. Resolvins are part of a large family of specialized pro-resolving lipid mediators that enhance active resolution of inflammation and return of inflammatory lesions to homeostasis. In this paper, we demonstrate that resolvin D2 (RvD2), a product of docosahexaenoic acid (DHA) metabolism, prevents alveolar bone loss in Porphyromonas gingivalis-induced experimental periodontitis. Investigations of the immune mechanism of RvD2 actions reveal that 6 weeks after infection, the gingiva of RvD2-treated mice exhibit decreased CD4+ T-cells as well as lower RANKL expression levels and higher osteoprotegerin expression levels. Systemically, RvD2 prevents chronic secretion of IFN-γ and rapidly restores IFN-α levels, without dampening the P. gingivalis-specific immune response. In the gingiva, immediately after P. gingivalis inoculation, RvD2 regulates the mRNA expression of IFN-γ, IL-1β, TNF-α, and IL-10, hence contributing to maintaining local homeostasis. Moreover, RvD2 treatment reduces local neutrophil numbers, whereas pro-resolving macrophage counts were increased. These findings suggest that RvD2 resolves innate inflammatory responses, inhibiting systemic and gingival Th1-type adaptive responses that are known to mediate alveolar bone loss in this model.
Highlights
Periodontitis is a chronic, polymicrobial infectious-inflammatory disease of the supporting structures of the teeth [1]
These results suggest that resolvin D2 (RvD2) modulates the RANKL/OPG axis, and prevents further alveolar bone loss
We demonstrate that the D-series resolvin, RvD2, is protective against P. gingivalis induced periodontal bone loss in the mouse
Summary
Periodontitis is a chronic, polymicrobial infectious-inflammatory disease of the supporting structures of the teeth [1]. The concentrations of IFN-γ are significantly higher in serum samples and gingival tissue biopsies obtained from periodontitis patients compared to people without periodontitis [4]. High levels of IFN-α have been reported in the gingiva of people with periodontitis compared to people without periodontitis [5], as well as in the plasma [6, 7]. Peripheral blood neutrophils obtained from people with active periodontitis have an hyperactive phenotype that is consistent with the IFN-α signature in their blood [6]. We have shown in a murine model of P. gingivalis-induced experimental periodontitis that diseased mice produce high levels of IFN-γ and highly express type-1 IFNs for a
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