黏附分子与炎症在委内瑞拉马脑炎病毒感染鼠脑中的作用

BACKGROUND

Neuroinvasion of Venezuelan equine encephalitis virus (VEEV) and subsequent initiation of inflammation in the brain plays a crucial role in the outcome of VEEV infection in mice. Adhesion molecules expressed on microvascular endothelial cells in the brain have been implicated in the modulation of the blood brain barrier (BBB) and inflammation in brain but their role in VEEV pathogenesis is not very well understood. In this study, we evaluated the expression of extracellular matrix and adhesion molecules genes in the brain of VEEV infected mice.

FINDINGS

Several cell to cell adhesion molecules and extracellular matrix protein genes such as ICAM-1, VCAM-1, CD44, Cadherins, integrins, MMPs and Timp1 were differentially regulated post-VEEV infection. ICAM-1 knock-out (IKO) mice infected with VEEV had markedly reduced inflammation in the brain and demonstrated a delay in the onset of clinical symptoms of disease. A differential regulation of inflammatory genes was observed in the IKO mice brain compared to their WT counterparts.

CONCLUSIONS

These results improve our present understanding of VEEV induced inflammation in mouse brain.

背景

委内瑞拉马脑炎病毒（VEEV）的神经侵袭以及随后在大脑中引发的炎症，在 VEEV 感染小鼠的结局中起着至关重要的作用。大脑微血管内皮细胞上表达的黏附分子被认为参与了血脑屏障（BBB）的调节和大脑中的炎症，但它们在 VEEV 发病机制中的作用还不是很清楚。在这项研究中，我们评估了 VEEV 感染小鼠大脑中细胞间黏附分子和细胞外基质蛋白基因的表达。

结果

几种细胞间黏附分子和细胞外基质蛋白基因，如 ICAM-1、VCAM-1、CD44、钙黏蛋白、整合素、MMPs 和 TIMP1，在 VEEV 感染后发生了差异调节。感染 VEEV 的 ICAM-1 敲除（IKO）小鼠大脑中的炎症明显减少，并表现出疾病临床症状发作的延迟。与 WT 小鼠相比，IKO 小鼠大脑中的炎症基因表达存在差异调节。