PMID- 21924184 OWN - NLM STAT- MEDLINE DCOM- 20120117 LR - 20110919 IS - 1878-3554 (Electronic) IS - 0099-2399 (Linking) VI - 37 IP - 10 DP - 2011 Oct TI - Up-regulation of nucleotide-binding oligomerization domain 1 in inflamed human dental pulp. PG - 1370-5 LID - 10.1016/j.joen.2011.06.008 [doi] AB - INTRODUCTION: The innate immune response is activated by recognition of microbial components through specific pattern recognition receptors including nucleotide-binding oligomerization domain (NOD)-like receptors. However, the regulation of NOD-1 in inflamed human dental pulp remains poorly understood. This study aimed to evaluate the expression of NOD-1 in healthy and inflamed human dental pulps. In addition, the secretion of chemokines induced by NOD-1 and the related signaling pathways were studied. METHODS: Samples of human dental pulp tissues were obtained from freshly extracted wisdom teeth. The protein localization of NOD-1 in the pulp tissues was detected by immunohistochemistry. In addition, human dental pulp fibroblasts were stimulated with NOD-1 agonist gamma-D-glutamylmeso-diaminopimelic acid. Production of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) was determined by an enzyme-linked immunosorbent assay. The involvement of mitogen-activated protein kinase (MAPK) signaling pathways was examined by Western blot analysis, and the association of MAPK signaling with chemokine production was determined. RESULTS: The results demonstrated the expression of NOD-1 in normal dental pulp, and up-regulated NOD-1 expression was observed in inflamed dental pulp. On stimulation with NOD-1 agonist, production of IL-8 and MCP-1 was induced in a dose-dependent manner. Moreover, phosphorylation of p38 MAPK and Jun N-terminal kinase (JNK) was enhanced by stimulation of NOD-1. With the treatment of p38 MAPK and JNK inhibitors, the NOD-1-induced IL-8 production was suppressed. CONCLUSIONS: In response to microbial invasion, the expression of NOD-1 can be regulated in a ligand-inducible manner. NOD-1 might participate in pulp inflammation through chemokine production via MAPK signaling pathways. CI - Copyright (c) 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved. FAU - Lee, Ya-Yun AU - Lee YY AD - Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan. FAU - Chan, Chi-Hang AU - Chan CH FAU - Hung, Shan-Ling AU - Hung SL FAU - Chen, Yi-Chen AU - Chen YC FAU - Lee, Yuan-Ho AU - Lee YH FAU - Yang, Shue-Fen AU - Yang SF LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110727 PL - United States TA - J Endod JT - Journal of endodontics JID - 7511484 RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-8) RN - 0 (NOD1 protein, human) RN - 0 (Nod1 Signaling Adaptor Protein) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) MH - Analysis of Variance MH - Cells, Cultured MH - Chemokine CCL2/biosynthesis/genetics MH - Dental Pulp/cytology/immunology/metabolism MH - Fibroblasts/immunology/metabolism MH - Gene Expression Regulation MH - Humans MH - Interleukin-8/*biosynthesis/genetics MH - JNK Mitogen-Activated Protein Kinases/metabolism MH - MAP Kinase Signaling System MH - Nod1 Signaling Adaptor Protein/agonists/*biosynthesis/genetics MH - Phosphorylation MH - Pulpitis/*immunology/*metabolism MH - Statistics, Nonparametric MH - Up-Regulation MH - p38 Mitogen-Activated Protein Kinases/metabolism EDAT- 2011/09/20 06:00 MHDA- 2012/01/18 06:00 CRDT- 2011/09/20 06:00 PHST- 2011/01/28 00:00 [received] PHST- 2011/06/02 00:00 [revised] PHST- 2011/06/03 00:00 [accepted] PHST- 2011/09/20 06:00 [entrez] PHST- 2011/09/20 06:00 [pubmed] PHST- 2012/01/18 06:00 [medline] AID - S0099-2399(11)00711-4 [pii] AID - 10.1016/j.joen.2011.06.008 [doi] PST - ppublish SO - J Endod. 2011 Oct;37(10):1370-5. doi: 10.1016/j.joen.2011.06.008. Epub 2011 Jul 27.