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

本研究的目的是探讨病毒感染后引起小鼠牙齿发育不良的机制。探讨了牙齿发育不全与系统性炎症之间的关系。给新生小鼠腹腔内（IP）接种小鼠巨细胞病毒（MCMV）史密斯株。处死小鼠并用扫描电镜观察其门牙。研究结果表明，病毒感染急性期形成的部位的门牙表面粗糙。然后，使用细胞因子微阵列检查细胞因子的表达。结果显示，病毒感染后IL-2、IL-4、IL-5、11-6、IL-10、IL-17、MCP-1、TPO、VEGF发生变化。对 Nest、作为组织炎症指标的组氨酸脱羧酶 (HDC) 活性动力学和细胞因子进行了研究。用 MCMV 腹膜内接种 4 周龄的小鼠。感染后1～13天，对各器官取样，分析其HDC活性和细胞因子水平。当 HDC 活性升高时，在脾脏和肝脏中分离出 MCMV。 HDC活性升高的时间过程在不同器官中是不同的。细胞因子动力学数据显示，脾脏中VEGF和TNF-α的水平显着下降。肝脏中IL-12、TNF-α、IL-6的水平显着升高。在肺中，IL-1 增加，IL-6 减少。 MCMV感染后第13天，IFN-γ水平升高。这些数据表明，病毒感染后宿主的炎症反应很大，并且在各个器官中持续了10天以上。趋化因子水平的改变可能会影响白细胞向病毒感染部位的迁移和激活。 HDC活性增强而产生的组胺，引起微循环系统的变化，血管通透性增强。综上所述，由于血管系统在牙齿形成过程中发挥作用，病毒感染后的系统炎症会影响牙齿的形成。

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.