Regulation of oral mucosal immunity in human oral epithelial cells and periodontitis

人口腔上皮细胞口腔黏膜免疫调节与牙周炎

• 批准号: 13671894
• 负责人: SUGAWARA Shunji
• 金额: $ 2.3万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671894/
• 关键词: oral epithelial cells; mucosal immunity; cytokines; fibroblasts; saliva; innate immunity; neutrophil proteinases; periodontitis; プロテアーゼ活性化受容体; 菌体成分

1. Oral epithelial cells constitutively express precursor form of interleukin-18 (IL-18) in the cells. Bioactive IL-18 was produced from the cells on costimulation with neutrophil serine proteinase, proteinase 3 (PR3), and Iipopolysaccharide (LPS) after interferon-γ (IFN-γ)-priming. PR3 was found to activate oral epithelial cells through G protein-coupled protease-activated receptor-2.2. Oral epithelial cells do not express a bacterial pattern recognition receptor, CD 14, and express Toll-like receptors (TLRs)/MD-2/MyD88 system, which is critical in innate immune recognition. However, the cells are refractory to bacterial components even in the presence of soluble CD14, The cells are able to respond to components from black-pigmented bacteria (BPB). The cells acquire responsiveness to many bacterial components after priming with IFN-γ.3. Nonendotoxic glycoprotein from BPB activates host cells in a CD14- and TLR2-dependent manner.4. CD14-expreswsing human gingival fibroblasts (HGF) have the same property with oral epithelial cells. Human periodontal ligament fibroblasts (HPLF) express TLR2 more strongly than HGF. HGF mainly respond to Gram-negative, and HPLF mainly respond to Gram-positive bacterial components, respectively. Cysteine proteinases (gingipains) from periodontopafhic bacteria degrade CD14 on HGF, consequently, suppress CD14-dependent responsiveness to bacterial components.5. Human salivary glands constitutively express CD14 and secrete as a soluble form in saliva.

1. 口腔上皮细胞组成性表达白细胞介素-18 （IL-18）的前体形式。在干扰素-γ (IFN-γ)启动后，细胞与中性粒细胞丝氨酸蛋白酶、蛋白酶3 （PR3）和ipopolaccharide （LPS）共刺激产生具有生物活性的IL-18。PR3通过G蛋白偶联蛋白酶激活受体2.2激活口腔上皮细胞。口腔上皮细胞不表达细菌模式识别受体cd14，表达toll样受体(TLRs)/MD-2/MyD88系统，这在先天免疫识别中至关重要。然而，即使在可溶性CD14存在的情况下，细胞对细菌成分也难以抵抗，细胞能够对来自黑色色素细菌（BPB）的成分做出反应。在IFN-γ.3启动后，细胞获得了对许多细菌成分的反应性。来自BPB的非内毒素糖蛋白以CD14-和tlr2依赖的方式激活宿主细胞。表达cd14的人牙龈成纤维细胞（HGF）与口腔上皮细胞具有相同的特性。人牙周韧带成纤维细胞（HPLF）比HGF表达TLR2更强烈。HGF主要响应革兰氏阴性菌成分，HPLF主要响应革兰氏阳性菌成分。来自牙周病细菌的半胱氨酸蛋白酶（gingipains）降解HGF上的CD14，从而抑制CD14对细菌成分的依赖性反应。人类唾液腺组成性表达CD14并以可溶性形式在唾液中分泌。

项目成果

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Sugawgr，S.，S.Yang，K.Iki，J.Hatakeyama，R.Tamai，O.Takeuchi，S.Akashi，T.Espevik，S.Akira，H.Takada：“来自普雷沃菌的非内毒性糖蛋白激活单核细胞

Sugawara,S., A.Uehara, T.Nochi, T.Yamaguchi, H.Ueda, K.Hanzawa, A.Sugiyama, K.Kumagai, H.Okamura, H.Takada: "Neutrophil proteinase 3 mediated induction of bioactive IL-18 secretion by human oral epithelial cells"J. Immunol.. 167-11. 6568-6575 (2001)

Sukawara,S., A.Uehara, T.Nochi, T.Yamaguchi, H.Ueda, K.Hanzawa, A.Sugiyama, K.Kumagai, H.Okamura, H.Takada：“中性粒细胞蛋白酶 3 介导的生物活性 IL 的诱导

Tada,H., S.Sueawara, E.Nemoto, N.Takahashi, T.Imamura, J.Potempa, J.Travis, R.Shimauchi, H.Takada: "Proteolysis of CD14 on human gingival. fibroblasts by arginine-specific cysteine proteinases from Porphyromonas gingivalis leadinjg to down-regulation of l

Tada,H., S.Sueawara, E.Nemoto, N.Takahashi, T.Imamura, J.Potempa, J.Travis, R.Shimauchi, H.Takada：“通过精氨酸特异性对人牙龈上的 CD14 进行蛋白水解。成纤维细胞

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