Innate immune system in oral mucosa, with special reference to inhibition of inflammatory and immune responses and up-regulation of antibacterial functions

口腔粘膜的先天免疫系统，特别是抑制炎症和免疫反应以及上调抗菌功能

基本信息

批准号：
18390484
负责人：
TAKADA Haruhiko
金额：
$ 11.28万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

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.

在先天免疫系统中，微生物的常见和特殊结构、病原体相关分子模式 (PAMP) 可以被宿主细胞中的模式识别分子 (PRM) 识别，例如 Toll 样受体 (TLR) 和 NOD1/2。检查了口腔和相关粘膜的先天免疫系统，得到以下发现：1）口腔和各种上皮细胞（总共16个衬里细胞）表达TLR2和4。细胞表面和细胞内的 TLR3、7、NOD1 和 NOD2 上皮细胞在各自的合成配体刺激后一般不分泌炎症细胞因子，而细胞会主动产生抗菌因子，例如肽聚糖识别蛋白（PGRP-L、Iα、Iβ）。，S) 和 β-防御素 2。这些发现表明，与正常菌群中的各种微生物相互作用的上皮细胞受到负控制，以防止诱导过度炎症和免疫反应，同时它们积极产生抗微生物因子 2) 与 TLR 和 NOD1/2 配体联合刺激可协同诱导口腔上皮细胞中的抗微生物因子 3) 据报道，最小的 NOD1 配体是 iE-。 DAP [γ-D-谷氨酰-内消旋-二氨基庚二酸 (γ-D-Glu-meso-DAP)] 我们证明了内消旋-DAP。内消旋羊毛硫氨酸本身通过 NOD1 激活各种人类上皮细胞。当对耐药细胞进行处理以增加其通透性时，内消旋 DAP 明显激活了细胞，这表明内消旋 DAP 足以激活 NOD1 和 D-Glu 部分。 NOD 配体融入细胞需要 4) 另一方面，从正常菌群中分离的人牙龈成纤维细胞表达 TLR1-9 和NOD1/2，并在用相应的合成配体刺激后积极产生炎症细胞因子。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Antibodies against protease 3 prime human monocytic cells in culture in a protease-activated receptor 2- and NF-κB-dependent manner for various Toll-like receptor-, NOD1-, and NOD2-mediated activation

蛋白酶 3 抗体以蛋白酶激活受体 2 和 NF-κB 依赖性方式启动培养中的人单核细胞，以实现各种 Toll 样受体、NOD1 和 NOD2 介导的激活

DOI：
发表时间：
2007
期刊：
Interface Oral Health Science (M. Watanabe & O. Okuno (ed.)) (Springer, Tokyo)
影响因子：
0
作者：
Uehara. A.. T. Sato;S. Yokota;A Iwashiro;and H. Takada.
通讯作者：
and H. Takada.

Synergism between TLRs and NOD1/2 in oral epithelial cells.

口腔上皮细胞中 TLR 和 NOD1/2 之间的协同作用。