Journal
FRONTIERS IN IMMUNOLOGY
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.00785
Keywords
specialized pro-resolving lipid mediators; resolvin; periodontitis; alveolar bone loss; immune response
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Funding
- US-Israel Bi-National Grant [2011465]
- National Institute of Dental and Craniofacial Research USPHS [DE025020, DE025383]
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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-gamma and rapidly restores IFN-alpha levels, without dampening the P. gingivalis-specific immune response. In the gingiva, immediately after P. gingivalis inoculation, RvD2 regulates the mRNA expression of IFN-gamma, IL-1 beta, TNF-alpha, 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.
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