Pro-Inflammatory Effects of Interleukin-17A on Vascular Smooth Muscle Cells Involve NAD(P)H-Oxidase Derived Reactive Oxygen Species
Pro-Inflammatory Effects of Interleukin-17A on Vascular Smooth Muscle Cells Involve NAD(P)H-Oxidase Derived Reactive Oxygen Species
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DOI：
10.1159/000317400
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发表时间：
2011-01-01
影响因子：
1.7
通讯作者：
Kuhlmann, Christoph R. W.
中科院分区：
文献类型：
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作者：
Pietrowski, Eweline;Bender, Bianca;Kuhlmann, Christoph R. W.
众所周知，T细胞与动脉粥样硬化的炎症因素有关。最近，有研究表明Th17衍生的细胞因子IL-17参与血管平滑肌细胞（VSMC）的促炎反应。本研究的目的是研究活性氧（ROS）是否可能参与这种情况。采用荧光染料2'7'-二氯二氢荧光素（H2DCF）检测IL-17A对小鼠原发性VSMC中ROS生成的影响。IL-17A诱导VSMC中H2DCF荧光增加，该作用被NAD(P) h -氧化酶抑制剂apocynin和靶向Nox2的siRNA阻断。p38-MAPK抑制剂SB203580和SB202190剂量依赖性地减少IL-17A诱导的ROS产生。通过Luminex技术检测，IL-17A诱导的促炎细胞因子IL-6、G-CSF、GM-CSF和MCP-1的释放被NAD(P) h -氧化酶抑制完全消除。综上所述，我们的数据表明，IL-17A导致NAD(P) h -氧化酶依赖的ROS生成，导致VSMC的促炎激活。版权所有：S. Karger AG，巴塞尔
T cells are known for their contribution to the inflammatory element of atherosclerosis. Recently, it has been demonstrated that the Th17 derived cytokine IL-17 is involved in the pro-inflammatory response of vascular smooth muscle cells (VSMC). The aim of the present study was to examine whether reactive oxygen species (ROS) might be involved in this context. The effect of IL-17A on ROS generation was examined using the fluorescent dye 2'7'-dichlorodihydrofluorescein (H2DCF) in primary murine VSMC. IL-17A induced an increase in H2DCF fluorescence in VSMC, and this effect was blocked by the NAD(P) H-oxidase inhibitor apocynin and siRNA targeting Nox2. The p38-MAPK inhibitors SB203580 and SB202190 dose-dependently reduced the IL-17A induced ROS production. The IL-17A induced release of the pro-inflammatory cytokines IL-6, G-CSF, GM-CSF and MCP-1 from VSMC, as detected by the Luminex technology, was completely abolished by NAD(P) H-oxidase inhibition. Taken together, our data indicate that IL-17A causes the NAD(P) H-oxidase dependent generation of ROS leading to a pro-inflammatory activation of VSMC. Copyright (C) 2010 S. Karger AG, Basel