IADR Abstract Archives
Immune Modulation by Resolvin D2 Prevents Experimental Periodontitis
Objectives: 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, which actively promote tissue repair, bacterial clearance and enhance protective host responses. This study aims to characterize the mechanism by which resolvin D2 (RvD2) regulates immunological functions during experimental periodontitis.
Methods: Experimental periodontitis was induced in mouse by three oral gavages two days a part with Porphyromonas gingivalis 53977 (Pg). The test group was treated intraperitoneally with 0.5 µg of RvD2 simultaneously with oral gavages and maintained with six additional doses of 0.1 µg RvD2 during the 2 weeks post-infection. Control mice received saline intraperitoneally at the same time points. Six weeks after infection, alveolar bone loss (ABL) was quantified using μCT, RANKL and OPG levels were assessed by ELISA and qPCR. Gingival immune cells were analyzed by flow cytometry. Systemic T cell functions were assessed after cell culture.
Results: RvD2 prevents ABL in a setting of experimental periodontitis by shifting the RANKL/OPG ratio in the gingiva. Six weeks after infection, the gingiva of RvD2-treated mice exhibit decreased frequencies of CD4+ T cells as well as lower Treg number. Systemically, RvD2 prevents chronic secretion of IFN-γ and rapidly restores IFN-α levels, without dampening the Pg-specific immune response. Immediately after infection, RvD2 maintains gingival homeostasis by controlling expression of IFN-γ, TNF-α, IL-1β and IL-10. Moreover, RvD2 treatment reduces neutrophil immigration, and promotes M2 macrophage polarization.
Conclusions: Exogenous administration of RvD2 during experimental periodontitis inhibits the development of inflammatory destructive immune responses and prevents the associated ABL. Elucidating the mechanism by which RvD2 modulates inflammation during experimental periodontitis, will contribute to the development of future preventive measures and treatment modalities for human periodontitis.
Methods: Experimental periodontitis was induced in mouse by three oral gavages two days a part with Porphyromonas gingivalis 53977 (Pg). The test group was treated intraperitoneally with 0.5 µg of RvD2 simultaneously with oral gavages and maintained with six additional doses of 0.1 µg RvD2 during the 2 weeks post-infection. Control mice received saline intraperitoneally at the same time points. Six weeks after infection, alveolar bone loss (ABL) was quantified using μCT, RANKL and OPG levels were assessed by ELISA and qPCR. Gingival immune cells were analyzed by flow cytometry. Systemic T cell functions were assessed after cell culture.
Results: RvD2 prevents ABL in a setting of experimental periodontitis by shifting the RANKL/OPG ratio in the gingiva. Six weeks after infection, the gingiva of RvD2-treated mice exhibit decreased frequencies of CD4+ T cells as well as lower Treg number. Systemically, RvD2 prevents chronic secretion of IFN-γ and rapidly restores IFN-α levels, without dampening the Pg-specific immune response. Immediately after infection, RvD2 maintains gingival homeostasis by controlling expression of IFN-γ, TNF-α, IL-1β and IL-10. Moreover, RvD2 treatment reduces neutrophil immigration, and promotes M2 macrophage polarization.
Conclusions: Exogenous administration of RvD2 during experimental periodontitis inhibits the development of inflammatory destructive immune responses and prevents the associated ABL. Elucidating the mechanism by which RvD2 modulates inflammation during experimental periodontitis, will contribute to the development of future preventive measures and treatment modalities for human periodontitis.