Xia Yun, Yamagata Kanato, Krukoff Teresa L
Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada T6G 2H7.
Brain Res. 2006 Jun 20;1095(1):85-95. doi: 10.1016/j.brainres.2006.03.112. Epub 2006 May 12.
The CD14/toll-like receptor 4 (TLR4) complex plays a vital role in initiating lipopolysaccharide (LPS) signaling during inflammation. In this study, we assessed innate immune responses and inflammatory transmission in the rat brain following intracerebroventricular (i.c.v.) administration of LPS. I.c.v. LPS induced the widespread increase in CD14 mRNA but did not change levels of TLR4 transcription in the brain. An increase in TLR4 immunoreactivity, coincident with cell death, leukocyte infiltration and neural tissue damage, was found in the meninges, choroid plexus and ventricular ependyma. In addition to CD14, rapid increases in gene expression of IkappaBalpha, IL-1beta, and TNF-alpha occurred along the meninges and ventricular ependyma. The response was most intense along the borders of the brain and declined in intensity in the adjacent periventricular areas and cerebral cortex. In the brain parenchyma, increased TLR4 immunoreactivity was confined to the vasculature and neighboring tissues along with strong vascular expression of IkappaBalpha and mPGES-1. These results suggest involvement of TLR4 in both brain inflammation and neural tissue injury and support the hypothesis that local diffusion and vascular transmission of inflammatory molecules are two major routes for developing inflammation in the brain.
CD14/ Toll样受体4（TLR4）复合物在炎症过程中启动脂多糖（LPS）信号传导方面发挥着至关重要的作用。在本研究中，我们评估了脑室内（i.c.v.）注射LPS后大鼠脑中的先天免疫反应和炎症传播。脑室内注射LPS导致CD14 mRNA广泛增加，但并未改变脑中TLR4的转录水平。在脑膜、脉络丛和脑室室管膜中发现TLR4免疫反应性增加，同时伴有细胞死亡、白细胞浸润和神经组织损伤。除了CD14外，IκBα、IL-1β和TNF-α的基因表达在脑膜和脑室室管膜处迅速增加。这种反应在脑边界处最为强烈，在相邻的脑室周围区域和大脑皮层中强度下降。在脑实质中，TLR4免疫反应性增加仅限于血管系统和邻近组织，同时IκBα和mPGES-1在血管中强烈表达。这些结果表明TLR4参与了脑部炎症和神经组织损伤，并支持炎症分子的局部扩散和血管传播是脑部炎症发展的两个主要途径这一假说。
