Role of brain pericytes in migration of inflammatory cells across the blood-brain barrier

多发性硬化症是一种自身免疫性疾病，与炎性细胞穿过血脑屏障（BBB）浸润到脑实质中有关。脑周细胞是血脑屏障的细胞组成部分，与脑内皮细胞共享基底膜，维持血脑屏障的功能。然而，目前尚不清楚脑周细胞是否参与了炎症细胞浸润BBB的多个步骤。在这里，我们调查是否脑周细胞调节巨噬细胞的迁移和细胞粘附分子的表达，使用永生化小鼠脑内皮细胞（MBEC 4）单层和共培养与原代培养的大鼠脑周细胞。TNF-α剂量依赖性地增加MBEC 4细胞ICAM-1和VCAM-1的表达。周细胞抑制TNF-α诱导的ICAM-1和VCAM-1表达增加以及小鼠巨噬细胞系J774A.1细胞跨MBEC 4细胞的迁移。这些发现表明，脑周细胞通过抑制脑内皮细胞中炎性细胞因子诱发的细胞粘附分子表达来阻断炎性细胞穿过BBB的迁移。

Multiple sclerosis is an autoimmune disease and associated with the infiltration of inflammatory cells into the brain parenchyma across the blood-brain barrier (BBB). Brain pericytes, a cellular component of the blood-brain barrier (BBB), share the basement membrane with brain endothelial cells and maintain the BBB functions. However, it is unclear whether brain pericytes participate in multiple steps of the infiltration of inflammatory cells across the BBB. Here, we investigated whether brain pericytes regulate macrophage migration and the expression of cell adhesion molecules using immortalized mouse brain endothelial cells (MBEC4) monolayer and co-cultured with primary culture of rat brain pericytes. TNF-α dose-dependently increased the expression of ICAM-1 and VCAM-1 in MBEC4 cells. Pericytes inhibited these TNF-α-induced increases in ICAM-1 and VCAM-1 expression and the migration of J774A.1 cells, a mouse macrophage cell line, across MBEC4 cells. These findings suggest that brain pericytes block migration of the inflammatory cells across the BBB by inhibiting inflammatory cytokines-evoked expression of cell adhesion molecules in the brain endothelial cells.