Immunological studies on mechanism for teeth hypoplasia following virus infection in mouse model

病毒感染小鼠模型牙齿发育不全机制的免疫学研究

• 批准号: 17592127
• 负责人: MAYANAGI Hideaki
• 金额: $ 2.24万
• 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17592127/
• 关键词: teeth hypoplasia; infection; mouse Cytomegalovirus; cytokine; HDC activity; 歯の形成不全

The purpose of this study was to examine the mechanisms that teeth hypodisplasia of mice were caused following virus infection. The relationship between teeth hypoplasia and systematic inflammation was addressed.Newborn mice were inculated intraperitoneally (IP) with mouse cytomegalovirus (MCMV) smith strain. Mice were killed and their incisor teeth were observed with SEM. The findings showed that the surface of incisors were rough in the site formed in the acute phase of virus infection. Then, the cytokine expression was examined by using cytokine microarray. The results showed that IL-2, IL-4, IL-5, 11-6, IL-10, IL-17, MCP-1, TPO and VEGF changed after virus infection. Nest, kinetics of histidine decarboxylase (HDC) activities, as index of inflammation of tissues, and cytokine were studied. Four- weeks of age mice were inoculated IP with MCMV. On 1 to 13th days after the infection, various organs were sampled, and their HDC activities and the level of cytokines were analyzed. MCMV were isolated in spleen and liver when those HDC activity elevated. The time course that HDC activities elevate were different among organs. The data of cytokine kinetics showed that the levels of VEGF and TNF-α decreased significantly in spleen. In liver, the levels of IL-12, TNF-α, IL-6 increased significantly. In lung, IL-1 increased and IL-6 decreased. IFN-γ level increased on 13th after MCMV infection.These data suggested that host's inflammation response was big after virus infection, and continued over 10 days in various organs. Altered level of chemokines may influence the migration and activation of leukocytes to the site of virus infection. Histamine, produced by the result from enhancement of HDC activity, causes changes of micro-circulation system, enhances vascular permeability. In conclusion, as vascular system play a role in the teeth forming period, the systematic inflammation following virus infection affect teeth formation.

本研究旨在探讨病毒感染引起小鼠牙齿发育不良的机制。为探讨牙齿发育不良与全身炎症的关系，用小鼠巨细胞病毒(MCMV)Smith株对新生小鼠进行了腹腔接种。处死小鼠，用扫描电子显微镜观察小鼠的切牙。结果表明，在病毒感染急性期形成的部位，门牙表面粗糙。用细胞因子芯片检测细胞因子的表达。结果表明，病毒感染后IL-2、IL-4、IL-5、11-6、IL-10、IL-17、MCP-1、TPO和血管内皮生长因子均发生变化。Nest、作为组织炎症指标的组氨酸脱羧酶(HDC)活性和细胞因子的动态变化。4周龄小鼠ip接种巨细胞病毒。感染后1~13天，取各脏器，分析其HDC活性和细胞因子水平。当HDC活性升高时，在小鼠的脾和肝脏中分离到MCMV。不同器官HDC活性升高的时间进程不同。细胞因子动力学数据显示，脾组织中血管内皮生长因子和肿瘤坏死因子-α水平显著降低。肝脏IL-12、肿瘤坏死因子-α、IL-6水平显著升高。肺组织中IL-1升高，IL-6降低。干扰素-γ水平在感染巨细胞病毒后13天升高，提示病毒感染后宿主的炎症反应较大，并在各器官持续10天以上。趋化因子水平的改变可能影响白细胞向病毒感染部位的迁移和激活。HDC活性增强所产生的组胺可引起微循环系统的改变，增强血管通透性。总之，由于血管系统在牙齿形成期起作用，病毒感染后的全身炎症会影响牙齿的形成。