Periodontal Diseases as a Hypersensitivity Reaction Based on Innate Immune Responses in Periodontal Tissues

牙周病是一种基于牙周组织先天免疫反应的超敏反应

• 批准号: 14370576
• 负责人: TAKADA Haruhiko
• 金额: $ 9.41万
• 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: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370576/
• 关键词: Human gingival fibroblasts; Oral epithelial cells; Innate immunity; CD14; Toll-like receptor; NOD2; Gingipain; Protease-activated receptor; 線維芽細胞; 上皮細胞; 血小板; 歯肉繊維芽細胞; レクチン経路

We performed studies based on the hypothesis that "in periodontal tissues in which numerous bacteria inhabit and interact with the cells, host defense systems, especially innate immune systems, are activated constitutively, resulting in hypersensitivity-like reactions leading to tissue destruction and periodontal diseases". The major findings were as follows. 1)Innate immune responses of oral epithelial cells : Human oral epithelial cells could not respond to endotoxic lipopolysaccharide [LPS; Toll-like receptor (TLR) 4 ligand], peptidoglycans (PGN; TLR2 ligand), and muramyldipeptide (MDP; intracellular receptor, NOD2 was discovered in the last year), while they responded to some cell-surface components of periodontopathic bacteria. Interferon-γ(IFNγ)-treated human oral epithelial cells responded to various bacterial components to produce inflammatoty cytokines. 2)Innate immune responses of fibroblasts in periodontal tissues : Human gingival fibroblasts carrying membrane CD14 (mCD14) r … More esponded to LPS, while human periodontal ligament fibroblasts carrying much TLR2 but lacking mCD14 could not respond. to LPS, but responded to PGN. IFNγ-treated human gingival. fibroblasts exhibited marked response to-various bacterial components, accompanied by up-regulation of mCD14 and Myd88, which is a common adaptor molecule for TLRs. Gingipains produced by Porphyroinonas gingivalis cleaved mCD14 on human gingival fibroblasts, resulting in hypo-responsiveness to. LPS. 3)Soluble CD14 (sCD 14) in human saliva : Human salivary gland cells, especially parotid gland cells, produced sCD14: The sCD14 concentration in parotid saliva was comparable to that in human serum. Salivary sCD14-augmented the incorporation of Actinobacillus actinomycetemcomitans by oral epithel oral cells, resulting in the enhancement of the innate immune responses of the cells. 4)TLR4 agonistic activity of fungal mannan : Fungal cell-wall mannan, including that from oral Candida albicans, activated human monocytic cells in a CD14-and TLR4-dependent manner. Less

我们基于以下假设进行研究：“在大量细菌栖息并与细胞相互作用的牙周组织中，宿主防御系统，特别是先天免疫系统被组成性激活，导致过敏样反应，导致组织破坏和牙周疾病”。主要调查结果如下。 1）口腔上皮细胞的先天免疫反应：人类口腔上皮细胞不能对内毒素脂多糖[LPS；LPS； Toll 样受体 (TLR) 4 配体]、肽聚糖（PGN；TLR2 配体）和胞壁酰二肽（MDP；细胞内受体，去年发现的 NOD2），同时它们对牙周病细菌的一些细胞表面成分做出反应。干扰素-γ (IFNγ) 处理的人口腔上皮细胞对各种细菌成分作出反应，产生炎症细胞因子。 2）牙周组织成纤维细胞的先天免疫反应：携带膜CD14（mCD14）的人牙龈成纤维细胞对LPS有反应，而携带大量TLR2但缺乏mCD14的人牙周膜成纤维细胞则无法做出反应。向 LPS，但对 PGN 做出响应。 IFNγ处理过的人牙龈。成纤维细胞对各种细菌成分表现出明显的反应，并伴有 mCD14 和 Myd88（TLR 的常见接头分子）的上调。牙龈卟啉单胞菌产生的牙龈痛会裂解人牙龈成纤维细胞上的 mCD14，导致对牙龈的反应低下。脂多糖。 3）人唾液中的可溶性CD14（sCD 14）：人唾液腺细胞，特别是腮腺细胞产生sCD14：腮腺唾液中的sCD14浓度与人血清中的浓度相当。唾液 sCD14 增强了口腔上皮细胞对伴放线放线杆菌的掺入，从而增强了细胞的先天免疫反应。 4）真菌甘露聚糖的TLR4激动活性：真菌细胞壁甘露聚糖，包括来自口腔白色念珠菌的甘露聚糖，以CD14和TLR4依赖性方式激活人类单核细胞。较少的

项目成果

Uehara A, S Sugawara, H Takada: "Priming of human oral epithelial cells by interferon-γ to secrete cytokines in response to lipopolysaccharides, lipoteichoic acids and peptidoglycans."Journal of Medical Microbiology. 51-8. 626-634 (2002)

Uehara A、S Sugara、H Takada：“干扰素-γ 引发人口腔上皮细胞分泌细胞因子以响应脂多糖、脂磷壁酸和肽聚糖。”医学微生物学杂志 51-634 (2002)。

Uehara A, Sugawara S, Takada H.: "Priming of human oral epithelial cells by interferon-γ to secrete cytokines in response to lipopolysaccharides, lipoteichoic acids and peptidoglycans"Journal of Medical Microbiology. 51-8. 626-634 (2002)

Uehara A、Sugara S、Takada H.：“干扰素-γ 引发人口腔上皮细胞分泌细胞因子以响应脂多糖、脂磷壁酸和肽聚糖”医学微生物学杂志 51-634 (2002)。

Hatakeyama J, Tamai R, Sugiyama A, Akashi S, Sugawara S, Takada H.: "Contrasting responses of human gingival and periodontal ligament fibroblasts to bacterial cell-surface components through the CD14/Toll-like receptor system"Oral Microbiology and Immunol

Hatakeyama J、Tamai R、Sugiyama A、Akashi S、Sugara S、Takada H.：“人牙龈和牙周膜成纤维细胞通过 CD14/Toll 样受体系统对细菌细胞表面成分的对比反应”口腔微生物学和免疫学

Tada H, E Nemoto, H Shimauchi, T Watanabe, T Mikami, T Masumoto, N Ohno, H Tamura, K Shibata, S Akashi, K Miyake, S Sugawara, H Takada: "Saccharomyces cerevisiae-and Candida albicans-derived mannan induced production of tumor necrosis factor alpha by huma

Tada H、E Nemoto、H Shimauchi、T Watanabe、T Mikami、T Masumoto、N Ohno、H Tamura、K Shibata、S Akashi、K Miyake、S Sukawara、H Takada：“酿酒酵母和白色念珠菌衍生的甘露聚糖诱导

Uehara A, S Sugawara, K Watanabe, S Echigo, M Sato, T Yamaguchi, H Takada: "Constitutive expression of a bacterial pattern recognition receptor, CD14, in human salivary glands and secretion as a soluble form in saliva"Clinical and Diagnostic Laboratory Im

Uehara A、S Sukawara、K Watanabe、S Echigo、M Sato、T Yamaguchi、H Takada：“细菌模式识别受体 CD14 在人类唾液腺中的组成型表达以及在唾液中以可溶形式分泌”临床和诊断实验室