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

我们进行的研究基于这样的假设：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，特别是天然免疫系统被结构性地激活，导致类似过敏反应，导致组织破坏和牙周病。主要研究结果如下。1)口腔上皮细胞的先天免疫反应：人口腔上皮细胞对内毒素脂多糖、多肽聚糖、胞内受体NOD2均无反应，而对牙周病细菌的某些细胞表面成分有反应。干扰素-γ(干扰素γ)处理的人口腔上皮细胞能对各种细菌成分产生致炎细胞因子。2)牙周组织成纤维细胞的先天免疫反应：携带CD14(MCD14)r…的人牙龈成纤维细胞而携带大量TLR2但缺乏mCD14的人牙周膜成纤维细胞对脂多糖无反应。对内毒素有反应，对PGN有反应。干扰素γ处理的人牙龈。成纤维细胞对多种细菌成分表现出明显的反应，并伴有TLRs的常见适配分子mCD14和MyD88的上调。牙龈卟啉单胞菌产生的牙龈痛能裂解人牙龈成纤维细胞上的mCD14，导致对。LP。3)唾液中可溶性CD14(SCD14)：人唾液腺细胞，尤其是腮腺细胞产生sCD14：腮腺唾液中sCD14浓度与人血清中sCD14浓度相当。唾液sCD14-促进口腔上皮细胞与伴生放线杆菌的结合，从而增强细胞的天然免疫应答。4)真菌甘露聚糖的TLR4激活活性：真菌细胞壁甘露聚糖，包括口腔白色念珠菌的甘露聚糖，以CD14和TLR4依赖的方式激活人单核细胞。较少

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