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BioMed Research International
Volume 2016, Article ID 9325436, 11 pages
http://dx.doi.org/10.1155/2016/9325436
Research Article

Functional Roles of NOD1 in Odontoblasts on Dental Pulp Innate Immunity

1Department of Conservative Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan
2Division of Endodontics and Restorative Dentistry, Department of Oral Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokura-kita, Kitakyushu, Fukuoka 803-8580, Japan

Received 15 June 2016; Revised 25 August 2016; Accepted 4 September 2016

Academic Editor: Satoshi Imazato

Copyright © 2016 Yuki Hosokawa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.