Milner Richard, Campbell Iain L
Department of Molecular and Experimental Medicine, MEM-132, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Mol Cell Neurosci. 2006 Dec;33(4):429-40. doi: 10.1016/j.mcn.2006.09.004. Epub 2006 Oct 13.
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 beta1 and beta4 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 beta4 and alpha5 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 beta4 and alpha5 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.
有证据表明，血管功能受细胞外基质（ECM）蛋白通过整合素介导的信号传导强烈调控。为了确定在慢性神经炎症期间脑血管上的整合素表达是否发生改变，我们检测了在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β1和β4整合素的表达。中枢神经系统中IL-6或IFN-α的慢性产生促进了β4和α5整合素亚基的血管表达，这主要由星形胶质细胞促成。细胞外基质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，β4和α5整合素的星形胶质细胞表达分别被IL-6和IFN-α显著上调，而这些整合素的内皮细胞表达未改变。这些结果表明星形胶质细胞通过上调整合素表达对IL-6和IFN-α作出反应。我们提出，在神经炎症期间，星形胶质细胞试图增加血脑屏障（BBB）处的黏附相互作用，以增强屏障完整性。
