Dataset Information

Resolvin D2 Restrains Th1 Immunity and Prevents Alveolar Bone Loss in Murine Periodontitis.

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-? and rapidly restores IFN-? levels, without dampening the P. gingivalis-specific immune response. In the gingiva, immediately after P. gingivalis inoculation, RvD2 regulates the mRNA expression of IFN-?, IL-1?, TNF-?, 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.

SUBMITTER: Mizraji G

PROVIDER: S-EPMC5996935 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Resolvin D2 Restrains Th1 Immunity and Prevents Alveolar Bone Loss in Murine Periodontitis.

Mizraji Gabriel G Heyman Oded O Van Dyke Thomas E TE Wilensky Asaf A

Frontiers in immunology 20180425

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 <i>Porphyromonas gingivalis-</i>induced experimental periodontitis. Investigations of t ...[more]

PMID: 29922275

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Project description:Periodontitis is characterized by the progressive destruction of tooth-supporting alveolar bone, which is mainly caused by chronic inflammation in response to persistent bacterial insult. It has recently become clear that the pathogenesis of periodontitis is associated with a high ratio of proinflammatory M1 (classically activated) macrophages to anti-inflammatory M2 (alternatively activated). To decrease the inflammatory activity, we locally delivered the C-C motif chemokine ligand 2 (CCL2) using controlled-release microparticles (MPs). CCL2 is known to promote chemotaxis of M0 or M2 phenotype macrophages to the inflamed site and induce M2 phenotype polarization locally. Our in vitro data showed that CCL2 increased the number of M2 phenotype macrophages, decreased TNF-? secretion, and enhanced chemotaxis of RAW264.7 cells toward CCL2 MPs. Moreover, we induced periodontal disease in 2 animal models through inoculation of Porphyromonas gingivalis and ligature around the murine molar. Micro-computed tomography analysis showed significant reduction of alveolar bone loss in the CCL2 MP treatment group when compared with a blank MP group and a no-treatment periodontitis group in both models. Immunohistologic analysis showed a significant increase in the M2 phenotype subset and a decrease in the M1 phenotype subset in the CCL2 MP group of the P. gingivalis-induced model. Also, in both models, tartrate-resistant acidic phosphatase staining showed significantly fewer numbers of osteoclasts in the CCL2 MP group in alveolar bone area. Moreover, quantitative polymerase chain reaction results showed a significant increase in IL-1RA (interleukin 1 receptor antagonist) mRNA expression and a decrease in RANKL (receptor activator of nuclear factor kappa-? ligand) mRNA expression in the CCL2 MP group in the ligature model. In summary, manipulation of endogenous M2 phenotype macrophages with CCL2 MPs decreased the M1 phenotype:M2 phenotype ratio and prevented alveolar bone loss in mouse periodontitis models. The delivery of CCL2 MPs provides a novel approach to treat periodontal disease.

Dataset Information

Resolvin D2 Restrains Th1 Immunity and Prevents Alveolar Bone Loss in Murine Periodontitis.

Publications

Resolvin D2 Restrains Th1 Immunity and Prevents Alveolar Bone Loss in Murine Periodontitis.

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