Increased expression of the β4 and α5 integrin subunits in cerebral blood vessels of transgenic mice chronically producing the pro-inflammatory cytokines IL-6 or IFN-α, in the central nervous system
Increased expression of the β4 and α5 integrin subunits in cerebral blood vessels of transgenic mice chronically producing the pro-inflammatory cytokines IL-6 or IFN-α, in the central nervous system
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DOI：
10.1016/j.mcn.2006.09.004
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发表时间：
2006-12-01
影响因子：
3.5
通讯作者：
Campbell, Iain L.
中科院分区：
文献类型：
--
作者：
Milner, Richard;Campbell, Iain L.
有证据表明，血管功能强烈调节细胞外基质（ECM）蛋白通过整合素介导的信号。为了确定在慢性神经炎症过程中脑血管上整合素的表达是否改变，我们检测了星形胶质细胞产生促炎细胞因子白细胞介素-6（IL-6）或干扰素-α（IFN-α）的转基因小鼠中β 1和β 4整合素的表达。CNS中IL-6或IFN-α的慢性产生促进β 4和α 5整联蛋白亚基的血管表达，这主要由星形胶质细胞贡献。ECM配体层粘连蛋白和纤连蛋白的血管表达也增加。细胞培养研究表明，星形胶质细胞的β 4和α 5整合素的表达分别被IL-6和IFN-α显著上调，而这些整合素的内皮表达没有变化。这些结果表明星形胶质细胞通过上调整联蛋白表达来响应IL-6和IFN-α。我们提出，在神经炎症，星形胶质细胞试图增加粘附在血脑屏障（BBB）的相互作用，以增加屏障的完整性。(c)2006年爱思唯尔公司All rights reserved.
Evidence suggests that vascular function is strongly regulated by extracellular matrix (ECM) proteins via integrin-mediated signaling. To determine whether integrin expression on cerebral blood vessels is altered during chronic neuroinflammation, we examined beta 1 and beta 4 integrin expression in transgenic mice with astrocyte production of the pro-inflammatory cytokines interleukin-6 (IL-6) or interferon-alpha (IFN-alpha). Chronic production of IL-6 or IFN-alpha in the CNS promoted vascular expression of the beta 4 and alpha 5 integrin subunits, and this was contributed mostly by astrocytes. Vascular expression of the ECM ligands laminin and fibronectin was also increased. Cell culture studies showed that astrocyte expression of the beta 4 and alpha 5 integrins was significantly upregulated by IL-6 and IFN-alpha, respectively, while endothelial expression of these integrins was unchanged. These results show that astrocytes respond to IL-6 and IFN-alpha by upregulating integrin expression. We propose that during neuroinflammation, astrocytes attempt to increase adhesive interactions at the blood-brain barrier (BBB), in order to increase barrier integrity. (c) 2006 Elsevier Inc. All rights reserved.