Differential expression of the CD14/TLR4 complex and inflammatory signaling molecules following i.c.v. administration of LPS
Differential expression of the CD14/TLR4 complex and inflammatory signaling molecules following i.c.v. administration of LPS
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DOI：
10.1016/j.brainres.2006.03.112
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发表时间：
2006-06
期刊：
影响因子：
2.9
通讯作者：
Yun Xia;K. Yamagata;T. L. Krukoff
中科院分区：
文献类型：
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作者：
Yun Xia;K. Yamagata;T. L. Krukoff
CD 14/Toll样受体4（TLR 4）复合物在炎症过程中启动脂多糖（LPS）信号传导中起着至关重要的作用。在这项研究中，我们评估了大鼠脑室内（i. c. v.）给予LPS。I. c. v. LPS诱导CD 14 mRNA的广泛增加，但不改变脑中TLR 4转录水平。在脑膜、脉络丛和室管膜中发现TLR 4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CD 14外，IκBα、IL-1β和TNF-α的基因表达也在沿着脑膜和室管膜迅速增加。反应最强烈的沿着边界的大脑和强度下降，在邻近的脑室周围地区和大脑皮层。在脑实质中，增加的TLR 4免疫反应性仅限于血管和邻近组织沿着具有IκBα和mPGES-1的强血管表达。这些结果表明TLR 4参与脑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递是脑中发生炎症的两个主要途径的假设。
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 IκBα, IL-1β, and TNF-α 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 IκBα 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.