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

脑周细胞在炎症细胞跨血脑屏障迁移中的作用

• 批准号: 21790257
• 负责人: DOHGU Shinya
• 金额: $ 2.75万
• 依托单位: Fukuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790257/
• 关键词: 炎症・免疫; 脳ペリサイト; サイトカイン; ケモカイン; ICAM-1; VCAM-1; 血液脳関門; TNF-α; 浸潤

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.

多发性硬化症是一种自身免疫性疾病，与炎症细胞通过血脑屏障（BBB）浸润到脑实质有关。脑周细胞是血脑屏障（BBB）的一种细胞成分，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炎症细胞跨血脑屏障浸润的多个步骤。本研究利用永生化小鼠脑内皮细胞（MBEC4）单层细胞与原代培养的大鼠脑周细胞共培养，研究了脑周细胞是否调节巨噬细胞的迁移和细胞粘附分子的表达。TNF-α剂量依赖性地增加MBEC4细胞中ICAM-1和VCAM-1的表达。周细胞抑制TNF-α-诱导的ICAM-1和VCAM-1表达的增加以及小鼠巨噬细胞系J774A.1细胞在MBEC4细胞中的迁移。这些发现表明，脑周细胞通过抑制炎症细胞因子在脑内皮细胞中引起的细胞粘附分子的表达来阻止炎症细胞在血脑屏障中的迁移。

项目成果

炎症細胞の脳浸潤における脳ペリサイトの役割

脑周细胞在炎症细胞脑浸润中的作用

• 发表时间: 2011
• 作者: 一木奈津子、道具伸也;他6名
• 通讯作者: 他6名

Regulation of MMP-9 production in the brain pericytes.

大脑周细胞中 MMP-9 产生的调节。

• 发表时间: 2009
• 作者: 森麻美;花田真幸;坂本謙司;中原努;石井邦雄;道具伸也
• 通讯作者: 道具伸也