title: Functional Roles of NOD1 in Odontoblasts on Dental Pulp Innate Immunity.
abstract: Caries-related pathogens are first recognized by odontoblasts and induce inflammatory events that develop to pulpitis. Generally, initial sensing of microbial pathogens is mediated by pattern recognition receptors, such as Toll-like receptor and nucleotide-binding oligomerization domain (NOD); however, little is known about NODs in odontoblasts. In this study, the levels of NODs expressed in rat odontoblastic cell line, KN-3, were assessed by flow cytometry and the levels of chemokines in NOD-specific ligand-stimulated KN-3 cells were analyzed by real-time PCR and ELISA. The signal transduction pathway activated with NOD-specific ligand was assessed by blocking assay with specific inhibitors and reporter assay. In KN-3 cells, the expression level of NOD1 was stronger than that of NOD2 and the production of chemokines, such as CINC-1, CINC-2, CCL20, and MCP-1, was upregulated by stimulation with NOD1-specific ligand, but not with NOD2-specific ligand. CINC-2 and CCL20 production by stimulation with NOD1-specific ligand was reduced by p38 MAPK and AP-1 signaling inhibitors. Furthermore, the reporter assay demonstrated AP-1 activation in NOD1-specific ligand-stimulated KN-3 cells. These findings indicated that NOD1 expressed in odontoblasts functions to upregulate the chemokines expression via p38-AP-1 signaling pathway and suggested that NOD1 may play important roles in the initiation and progression of pulpitis.
authors.affiliation: Department of Conservative Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hosokawa
authors.affiliation: Department of Conservative Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Hirao
authors.affiliation: Department of Conservative Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan.
authors.forename: Hiromichi
authors.identifier: 0000-0002-8659-9776
authors.initials: H
authors.lastname: Yumoto
authors.affiliation: Division of Endodontics and Restorative Dentistry, Department of Oral Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokura-kita, Kitakyushu, Fukuoka 803-8580, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Washio
authors.affiliation: Department of Conservative Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nakanishi
authors.affiliation: Department of Conservative Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takegawa
authors.affiliation: Division of Endodontics and Restorative Dentistry, Department of Oral Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokura-kita, Kitakyushu, Fukuoka 803-8580, Japan.
authors.forename: Chiaki
authors.identifier: 0000-0002-1797-6988
authors.initials: C
authors.lastname: Kitamura
authors.affiliation: Department of Conservative Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuo
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000276:immunology*; D003782:Dental Pulp / Q000166:cytology* / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology; D053474:Nod1 Signaling Adaptor Protein / Q000276:immunology*; D009804:Odontoblasts / Q000166:cytology / Q000276:immunology*; D051381:Rats
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D053474:Nod1 Signaling Adaptor Protein