Dendritic cells maturation in the oral lichen planus as a target for treatment

口腔扁平苔藓中树突状细胞的成熟作为治疗目标

• 批准号: 16591841
• 负责人: KOMIYAMA Kazuo
• 金额: $ 2.3万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591841/
• 关键词: Oral lichen planus; T-cell; NK cell; s PLA2; COX2; Dendritic cell; mouse model; マウスモデル; Th1 cell; NK cell; PLA2; lichen planus; dendritc cell; sPL2; assaloGM1; flowcytometery; follicular dendrtic cell

Oral lichen planus is characterized histological by band-like T cells infiltration just under the basal cell layer of mucosal epithelium with unknown etiology. The Killer T and NK cell infiltration into the basal cell layer, indicated degeneration of basal cells. Dendritic cell (DC) found in the lesion of OLP may also important cell elements for controlling the lesion. However, the mechanism of these cells infiltration was not clarified yet. After DC migrated the lesion, DC revealed maturation by local synthesized arachidonate, PGE2. Thus, we made a plan to regulate DC function with suppression of arachidonate synthesis using histone deacethyrase inhibitor.We first examined cyclooxigenase 2 (COX2) and Phospholipase A2 expression of the OLP lesion, which relate to characteristic white color appearance on oral mucosa. COX2 over expression paralleled to thickness of epithelium and amounts of prickle cells in the epithelium. Clear finding obtained that subgroup specific PLA2, PLA2-V and PL … More A2-X but not for PLA2-IIa, were identified in the epithelium. In vitro experiment demonstrates dose dependent down regulate the PGE2 production by NaBu through the sPLA2 and COX2 expression. However, PGE2 play a role for the epithelial cell repair following epithelial cells received damage by CD8 positive cell and NK cells. More over the COX2 overexpression in the lesions may be related to malignant transformation of OLP. Thus, further experiments required elucidating critical mechanism for controlling the OLP. We also have developed a mouse experimental model of oral mucosal delayed type hyperplasia as a mimic of OLP. In this study, we have valuated the cells and cytokine involve development the OLP lesion for the development of useful treatment system. Our result clearly indicted that NK cell play key role for the early development of the lesion. NK cells deletion with asialo GM1 antibody administration indicated that mouse was clearly showed decrease the severity of DTH due to the disturbance of lymphocytes recruitment. IL-2 and INF-? are major cytokines involved in cell infiltration of the lesion. Less

口服地衣平面的特征是带状T细胞在粘膜上皮的基础细胞层下浸润，病因未知。杀伤剂T和NK细胞浸润到基础细胞层中，表明基本细胞的变性。在OLP病变中发现的树突状细胞（DC）也可能需要控制病变的重要细胞元素。但是，这些细胞的机制尚未阐明。 DC迁移病变后，DC揭示了局部合成的芳基丁酸盐的成熟，PGE2。这是我们制定了一个计划，使用组蛋白死亡蛋白酶抑制剂抑制蛛网膜合成，以调节直流功能。我们首先检查了OLP病变的环氧酶2（COX2）和磷脂酶A2表达，这与口服Mucosa上的特征性白色颜色相关。 COX2超过表达与上皮细胞的厚度和上皮细胞的量。明确发现，在上皮中鉴定出亚组特异性PLA2，PLA2-V和PL…更多A2-X，但对于PLA2-IIA，但没有鉴定出来。体外实验表明，剂量依赖于下调Nabu通过SPERA2和COX2表达的PGE2产生。然而，PGE2在上皮细胞后，PGE2对上皮细胞修复作用，受到CD8阳性细胞和NK细胞的损害。在病变中的COX2过表达上可能与OLP的恶性转化有关。这是进一步的实验需要阐明控制OLP的关键机制。我们还开发了一种小鼠粘膜延迟型增生的实验模型，作为OLP的模仿。在这项研究中，我们对细胞和细胞因子的评估涉及开发有用治疗系统的OLP病变。我们的结果清楚地指出，NK细胞在病变的早期发育中起关键作用。用Asialo GM1抗体给药删除NK细胞表明，由于淋巴细胞募集的灾难，明确显示了小鼠DTH的严重程度。 IL-2和INF-？是参与病变细胞浸润的主要细胞因子。较少的