2007 Fiscal Year Final Research Report Summary
Innate immune system in oral mucosa, with special reference to inhibition of inflammatory and immune responses and up-regulation of antibacterial functions
Project/Area Number |
18390484
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Morphological basic dentistry
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Research Institution | Tohoku University |
Principal Investigator |
TAKADA Haruhiko Tohoku University, Graduate School of Dentistry, Professor (30135743)
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Co-Investigator(Kenkyū-buntansha) |
UEHARA Akiko Graduate School of Dentistry, 大学院・歯学研究科, Assistant Professor (00431510)
SUGAWARA Yumiko University Hospital, 大学病院, Assistant Professor (30235866)
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Project Period (FY) |
2006 – 2007
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Keywords | Oral epithelial cells / Innate immunity / Toll-like receptor (TLR / NOD1 / NOD2 / β-Defensin 2 / Peptidoglycan recognition protein (PGRP) / Inflammatory response |
Research Abstract |
In the innate immune system, common and peculiar structures of microbes, pathogen-associated molecular patterns (PAMPs), are recognized by pattern-recognition molecules (PRMs) such as Toll-like receptors (TLRs) and NOD1/2 in host cells. We examined the innate immune system in the oral and related mucosa and obtained the following findings. 1) Oral and various epithelial cells (total of 16 lining cells) expressed TLR2 and 4 on the cell-surface and TLR3, 7, NOD1 and NOD2 intracellularly. The epithelial cells in general did not secrete inflammatory cytokines upon stimulation with respective synthetic ligands, whereas the cells actively produced antimicrobial factors such as peptidoglycan recognition proteins (PGRP-L, Iα, Iβ, S) and β-defensin 2. These findings suggest that epithelial cells, which interact with various microbes in normal flora, are negatively controlled to prevent the induction of excessive inflammatory and immune responses, while they actively produce anti-microbial factors. 2) Combined stimulation with TLR and NOD1/2 ligands synergistically induced anti-microbial factors in oral epithelial cells. 3) Minimal NOD1 ligand has been reported to be iE-DAP [γ-D-glutamy1-meso-diaminopimelic acid (γ-D-Glu-meso-DAP)]. We demonstrated that meso-DAP and meso-lanthionine by themselves activated various human epithelial cells via NOD1. When the resistant cells were treated to increase their permeability, meso-DAP clearly activated the cells, suggesting that meso-DAP is sufficient to activate NOD1 and that the D-Glu portion is required for the NOD-ligand to be incorporated into cells. 4) On the other hand, human gingival fibroblasts, which are isolated from normal flora, expressed TLR1-9 and NOD1/2, and actively produce inflammatory cytokines upon stimulation with the respective synthetic ligands.
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Research Products
(53 results)
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[Journal Article] Molecular cloning and functional characterization of porcine nucleotide-binding oligomerization domain-2 (NOD2).2008
Author(s)
Tohno, M., W. Ueda, Y. Azuma, T. Shimazu, S. Katoh, J.M. Wang, H. Aso, H. Takada, Y. Kawai, T. Saito, H. Kitazawa.
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Journal Title
Molecular Immunology 45
Pages: 194-203
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Molecular cloning and functional characterization of porcine nucleotide-binding oligomerization domain-1 (NOD1) recognizing minimum agonists, meso-diaminopimelic acid and meso-lanthionine.2008
Author(s)
Tohno, M., T. Shimazu, H. Aso, A. Uehara, H. Takada, A, Kawasaki, Y. Fujimoto, K. Fukase, T. Saito, H. Kitazawa.
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Journal Title
Molecular Immunology 45
Pages: 1807-1817
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Molecular cloning and functional characterization of porcine nucleotide-binding oligomerization domain-2 (NOD2)2008
Author(s)
Tohno, M., W. Ueda, Y. Azuma, T. Shimazu, S. Katoh, J.M. Wang, H. Aso, H. Takada. Y. Kawai, T. Saito, H. Kitazawa.
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Journal Title
Mol. Immunol 45-1
Pages: 194-203
Description
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[Journal Article] Toll-like receptors, NOD1, and NOD2 in oral epithelial cells2006
Author(s)
Sugawara, Y., A. Uehara, Y. Fujimoto, S. Kusumoto, K. Fukase, K. Shibata, S. Sugawara, T. Sasano, and H. Takada.
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Journal Title
Journal of Denal. Reearch. 85
Pages: 524-529
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Meso-diaminopimelic acid and meso-lanthionine, amino acids specific to bacterial peptidoglycans, activate human epithelial cells through NOD12006
Author(s)
Uehara, A, Y. Fujimoto, A, Kawasaki, S, Kusumoto, K, Fukase, and H, Takada.
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Journal Title
J. Immunol 177-3
Pages: 1796-1804
Description
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[Presentation] Antibodies to proteinase 3 (PR3) prime human monocytic cells in a protease-activated receptor (PAR)-2-, proteinase 3-, phospholipase C-, and NF-kB-dependent manner for CD14-, Toll-like receptor (TLR) 2-,3-,4-,7-,8-, NOD1-, and 2-mediated activation2006
Author(s)
Uehara, A., and H. Takada
Organizer
Joint Meeting of the Society for Leukocyte Biology and the International Endotoxin and Innate Immunity Society
Place of Presentation
San Antinio, Texas
Year and Date
20061109-11
Description
「研究成果報告書概要(和文)」より
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[Presentation] Constitutive expression of Toll-like receptors, NOD1, and NOD2 in Human oral epithelial cells and their function2006
Author(s)
Sugawara, Y., A. Uehara, Y. Fujimoto, S. Kusumoto, K. Fukase, K. Shibata, T. Sasano, and H. Takada.
Organizer
Joint Meeting of the Society for Leukocyte Biology and the International Endotoxin and Innate Immunity Society
Place of Presentation
San Antinio, Texas
Year and Date
20061109-11
Description
「研究成果報告書概要(和文)」より
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[Presentation] Antibodies to proteinase 3 (PR3) prime human monocytic cells in a protease-activated receptor (PAR)-2-, proteinase 3-, phospholipase C-, and NF-k_B-dependent manner for CD14-, Toll-like receptor (TLR)2-, 3-, 4-, 7-, 8-, NOD1-, and 2-mediated activation2006
Author(s)
Uehara. A., and H. Takada.
Organizer
Joint Meeting of the Society for Leukocyte Biology and the International Endotoxin and Innate Immunity Society
Place of Presentation
San Antion, Texaa
Year and Date
20061109-11
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Antibodies to proteinase 3 prime human monocytic cells via protease-activated preceptor-2, phospholipase C, and NF-kB for CD14-, Toll-like receptor 2-,3-,4-,7-,8-, NOD1-, and 2-dependent activation2006
Author(s)
Uehara, A., and H. Takada
Organizer
The 6th Awaji International Forum Infection and Immunity
Place of Presentation
Awaji, Hyogo
Year and Date
20060904-07
Description
「研究成果報告書概要(和文)」より
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[Book] Expression of various Toll-like receptors, NOD1, and NOD2, in human oral epithelial cells, and their function, In M. Watanabe & O. Okuno (ed.) Interface Oral Health Science 20072007
Author(s)
Sugawara, Y., A. Uehara, Y. Fujimoto, K. Fukase, T. Sasano, and H. Takada.
Total Pages
385(225-230)
Publisher
Springer, Tokyo
Description
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