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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

机译:长期在中枢神经系统中产生促炎细胞因子IL-6或IFN-α的转基因小鼠脑血管中β4和α5整联蛋白亚基的表达增加

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摘要

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 β1 and β4 integrin expression in transgenic mice with astrocyte production of the pro-inflammatory cytokines interleukin-6 (IL-6) or interferon-α (IFN-α). Chronic production of IL-6 or IFN-α in the CNS promoted vascular expression of the β4 and α5 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 β4 and α5 integrins was significantly upregulated by IL-6 and IFN-α respectively, while endothelial expression of these integrins was unchanged. These results show that astrocytes respond to IL-6 and IFN-α 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.
机译:有证据表明,通过整合素介导的信号传导,细胞外基质(ECM)蛋白强烈调节血管功能。为了确定在慢性神经炎症过程中脑血管上的整合素表达是否发生了改变,我们检查了星形胶质细胞产生促炎细胞因子白介素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)。 CNS中IL-6或IFN-α的长期产生促进了β4和α5整联蛋白亚基的血管表达,而这主要是由星形胶质细胞引起的。 ECM配体层粘连蛋白和纤连蛋白的血管表达也增加了。细胞培养研究表明,IL-6和IFN-α分别显着上调了β4和α5整合素的星形胶质细胞表达,而这些整合素的内皮表达未改变。这些结果表明星形胶质细胞通过上调整联蛋白表达而对IL-6和IFN-α起反应。我们建议在神经炎症过程中,星形胶质细胞试图增加血脑屏障(BBB)的黏附相互作用,以增加屏障的完整性。

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  • 期刊名称 other
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  • 年(卷),期 -1(33),4
  • 年度 -1
  • 页码 429–440
  • 总页数 22
  • 原文格式 PDF
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