| Co-Investigator(Kenkyū-buntansha) |
UEHARA Akiko Japan Society for the Promotion of Science, Research Fellow (PD), 特別研究員
FUNAYAMA Hitomi Tohoku University, Graduate School of Dentistry, Research Associate, 大学院・歯学研究科, 助手 (00359530)
SUGAWARA Shunji Tohoku University, Graduate School of Dentistry, Professor, 大学院・歯学研究科, 教授 (10241639)
TADA Hiroyuki Japan Society for the Promotion of Science, Research Fellow (PD), 特別研究員
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| Research Abstract |
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
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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
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