title: Tamibarotene modulates the local immune response in experimental periodontitis.
abstract: Tamibarotene (Am80), a synthetic retinoic acid receptor (RAR), is an agonist with high specificity for RARα and RARβ. Retinoid agonists have been shown to inhibit Th17 cell polarization and to enhance forkhead box P3 (Foxp3) expression during the course of inflammatory diseases. The aim of this study was to evaluate the previously unrecognized role of Am80 in regulating the immune responses of periodontitis within the oral microenvironment. The experimental model of periodontitis in mice was induced by oral infection with Porphyromonas gingivalis (P. gingivalis) W83. Our results indicated that Am80 effectively suppressed alveolar bone resorption induced by P. gingivalis W83 and decreased the number of osteoclasts. We clarified that these effects were closely associated with the reduced percentage of CD4(+) retinoid-related orphan receptor (ROR)γt(+) cells and increased the percentage of CD4(+) Foxp3(+) cells in the gingival tissues, cervical lymph nodes (CLNs), and spleen. Furthermore, in P. gingivalis-infected mice, Am80 down-regulated mRNA expression levels of interleukin-17A (IL-17A), receptor activator of nuclear factor-kappa beta ligand (RANKL), monocyte chemotactic protein-1 (MCP-1), IL-6, and IL-1β. Simultaneously, Am80 up-regulated expression levels of IL-10 and transforming growth factor-β1 (TGF-β1) in gingival tissues and the CLNs. Our results suggest that Am80 could protect against periodontal bone resorption, primarily through the modulation of immune responses in the oral microenvironment, and demonstrate the potential of Am80 as a novel clinical strategy for preventing periodontitis.
authors.affiliation: Department of Stomatology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Stomatology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Linyuan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Stomatology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Dixin
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Stomatology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. Electronic address: xiaoping_ba@126.com.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Lin
mesh_terms: D016301:Alveolar Bone Loss / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D016866:Bacteroidaceae Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D056747:Immunomodulation / Q000187:drug effects*; D008807:Mice, Inbred BALB C; D010518:Periodontitis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016966:Porphyromonas gingivalis; D018168:Receptors, Retinoic Acid / Q000819:agonists; D000072482:Retinoic Acid Receptor alpha; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D001565:Benzoates; D015415:Biomarkers; D016207:Cytokines; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D013764:Tetrahydronaphthalenes; C082925:retinoic acid receptor beta; C061133:tamibarotene
keywords: Bone resorption; Immunomodulation; Periodontitis; Tamibarotene; Th17 cells; Treg cells