Possible Role of Gingival Epithelial Cells in Host Immune Response of Periodontal Disease Progression

牙龈上皮细胞在牙周病进展的宿主免疫反应中的可能作用

• 批准号: 12672038
• 负责人: IZUMI Yuichi
• 金额: $ 2.18万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672038/
• 关键词: perodontal disease; gingival epithelial cells; immune response; CD 80; CD 86; MHC class II; prostaglandin; cyclooxygenase-2; 免疫応答

The purpose of the present research project was to clarify the possible role of gingival epithelial cells in host immune response of periodontal disease progression. Antigen presented by professional antigen-presenting cells (APC), which express both MHC class II and B7 costimulatory molecules, results in CD4+ T cell activation. In contrast, antigen presentation by MHC class II expressing non-professional APC which lack costimulatory molecules can render CD4+ T cells into a state of nonresponsiveness. In general, B7 costimulatory molecules are expressed by professional APC, such as macrophages or dendritic cells. Expression of MHC class II and B7-1 was detected on periodontal diseased human gingival epithelial tissue in situ by double color exposure confocal microscopy, but not in healthy gingival tissue. Also, two lines of rat gingival epithelial cells (GEC) demonstrated to constitutively expressed B7-1, but not B7-2 as analyzed by flow cytometry. By contrast, expression of MHC class II was only detected on both rat GEC klines after IFN-γ stimulation. Other rat non-professional APC such as endothelial cells or fibroblasts did not express B7-1 even after stimulation with IFN-γ. In order to elucidate the immunological significance of this ectopic B7-1 expression, antigen (Actinobacillus actinomycetemcomitans)-spedfic CD4+ Th1 T cell clones were cocultured with IFN-γ-/antigen-treated rat GEC. Consequently, the T cells became unresponsive to subsequent antigen-stimulation by professional APC as demonstrated by diminished proliferation. The induction of unresponsiveness was inhibited by anti-class II mAb or anti-CD80 mAb in the coculture of T clone cells and IFN-γ/antigen-treated GEC suggesting that GEC apparently present bacterial antigen, which resulted in T cell down regulation. These results suggest that ectopic expression of B7-1 by GEC may play a regulatory T cell to the commensal bacteria in the oral cavity in the context of a local inflammatory response.

本研究的目的是阐明牙龈上皮细胞在牙周病进展过程中宿主免疫反应中的可能作用。专业抗原提呈细胞(APC)同时表达MHC-II类和B7类共刺激分子，其提呈的抗原可导致CD4+T细胞的活化。相反，表达缺乏共刺激分子的非专业性APC的MHC-II类抗原呈递可使CD4+T细胞进入无应答状态。一般来说，B7共刺激分子是由专业的APC表达的，如巨噬细胞或树突状细胞。双色共聚焦显微镜原位检测到MHC-II和B7-1在牙周病患者牙龈上皮组织中的表达，而在正常牙周组织中未见表达。此外，两株大鼠牙龈上皮细胞(GEC)在流式细胞仪分析中均表达B7-1，但不表达B7-2。而在干扰素-γ刺激后，MHC-II类分子仅在两种大鼠肾小管上皮细胞系中均有表达。其他大鼠非专业性抗原原细胞，如内皮细胞或成纤维细胞，即使在干扰素-γ刺激后也不表达B7-1。为了阐明这种异位表达B7-1的免疫学意义，将抗原(伴放线放线杆菌)特异性的CD_4+Th1T细胞克隆与干扰素-γ-/抗原处理的大鼠肾小管上皮细胞共培养。结果，T细胞对专业APC随后的抗原刺激没有反应，表现为增殖减少。在T克隆细胞与干扰素-γ/抗原处理的GEC共培养中，抗II类单抗或抗CD80mAb可抑制无应答的诱导，提示GEC明显存在细菌抗原，从而导致T细胞下调。这些结果表明，GEC异位表达B7-1可能在局部炎症反应的背景下对口腔中的共生细菌起到调节T细胞的作用。

项目成果

Noguchi,Kazuyuki: "Downregulation of lipopolysaccharide -induced intercellular adhesion molecule-1 expression via EP2/EP4 receptors by prostaglandin E_2 in human fibroblasts"Inflammation. Vol. 25. 75-81 (2001)

Noguchi、Kazuyuki：“人成纤维细胞中前列腺素 E_2 通过 EP2/EP4 受体下调脂多糖诱导的细胞间粘附分子 1 表达”炎症。

Noguchi,Kazuyuki: "Upregulation of matrix metalloproteinase-1 production by prostaglandin F_2 alpha in human gingival fibroblasts"J. Periodont. Res.. Vol. 36. 334-339 (2001)

Noguchi，Kazuyuki：“人牙龈成纤维细胞中前列腺素 F_2 α 上调基质金属蛋白酶-1 的产生”J。

Kazuyuki Noguchi: "Involvement of cyclooxygenase-2 in serum-induced prostaglandin production by human oral gingival epithelial cells"J Periodont Res. 36. 124-130 (2001)

Kazuyuki Noguchi：“环氧合酶 2 参与血清诱导的人口腔牙龈上皮细胞产生前列腺素”J 牙周病研究。

Takashi Matsuyama: "Expression and activity of thrombomodulin in human gingival epithelium : in vivo and in vitro studies"J Periodont Res. 35. 146-157 (2000)

Takashi Matsuyama：“人牙龈上皮中血栓调节蛋白的表达和活性：体内和体外研究”J periodont Res。

Kazuyuki Noguchi: "Upregulation of matrix metalloproteinase-1 production by prostaglandin F_2 alpha in human gingival fibroblasts"J Periodont Res. 36. 334-339 (2001)

Kazuyuki Noguchi：“前列腺素 F_2 α 在人牙龈成纤维细胞中上调基质金属蛋白酶-1 的产生”J periodont Res。