Expression Analysis of Cytokine and Chemokine Genes during the Natural Course of Murine Experimental Autoimmune Uveoretinitis.
Expression Analysis of Cytokine and Chemokine Genes during the Natural Course of Murine Experimental Autoimmune Uveoretinitis.
复制标题
DOI：
10.5402/2012/471617
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Nishida K
中科院分区：
文献类型：
--
作者：
Hashida N;Ohguro N;Nishida K
用人光感受器间维甲酸结合蛋白肽免疫C57 BL/6小鼠，诱导实验性自身免疫性葡萄膜视网膜炎（EAU）。从免疫当天到30天后，每天从小鼠眼睛中分离RNA。以β-actin为内源性对照，采用TaqMan基因表达分析技术检测EAU发病过程中基因表达的动态变化，该方法包括大部分趋化因子/细胞因子及其受体、信号转导和转录激活因子（STAT）家族基因。基于其表达谱的基因簇进行分析，以确定炎症发病机制的候选基因。系统聚类分析显示EAU发育过程中的基因表达有7种聚类模式。层次聚类分析还确定了四个不同的阶段，在日常表达：入口，加速，减速和缓解。EAU活动期的基因表达变化显示Th 1型基因（IFN-γ和CXCL 10/IP-10）协同上调，Th 2型基因（CCL 17/TARC和IL-5）升高。STAT 1、STAT 6和STAT 3基因表达的顺序变化分别代表了Th 1、Th 2和Th 17型炎症基因的动态变化。STAT 1的表达模式是许多基因运动的代表。我们的研究结果表明，Th 1，Th 2和Th 17基因和STAT家族基因的协调作用参与EAU的发展和解决。
C57BL/6 mice were immunized with human interphotoreceptor retinoid-binding protein peptides to induce experimental autoimmune uveoretinitis (EAU). From the day of immunization to 30 days later, RNA was isolated daily from the mouse eyes. Dynamic changes in gene expression during the pathogenesis of EAU were analyzed by TaqMan gene expression assay that contained most chemokines/cytokines and their receptors, and signal transducer and activator of transcription (STAT) family genes, using beta-actin as the endogenous control. Gene clusters based on their expression profiles were analyzed to determine the candidate genes for the pathogenesis of inflammation. Hierarchical cluster analysis showed gene expression during EAU development in seven clustering patterns. Hierarchical cluster analysis also identified four distinct phases in daily expression: entrance, acceleration, deceleration, and remission. Gene expression changes in the EAU active phase showed synergetic upregulation of Th1-type genes (IFN-gamma and CXCL10/IP-10) with elevated Th2-type genes (CCL17/TARC and IL-5). Sequential expression changes of STAT1, STAT6, and STAT3 genes represented the dynamic changes of Th1, Th2, and Th17-type inflammatory genes, respectively. The expression pattern of STAT1 was representative of many gene movements. Our results suggested that coordinated action of Th1, Th2, and Th17 genes and STAT family genes are involved in EAU development and resolution.