INTERLEUKIN-8 - A MITOGEN AND CHEMOATTRACTANT FOR VASCULAR SMOOTH-MUSCLE CELLS
INTERLEUKIN-8 - A MITOGEN AND CHEMOATTRACTANT FOR VASCULAR SMOOTH-MUSCLE CELLS
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DOI：
10.1161/01.res.75.1.1
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发表时间：
1994-07-01
影响因子：
20.1
通讯作者：
FEUERSTEIN, GZ
中科院分区：
文献类型：
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作者：
YUE, TL;WANG, X;FEUERSTEIN, GZ
白细胞介素-8（IL-8）是由参与动脉粥样硬化形成的多种细胞类型产生的趋化因子，并且对中性粒细胞和淋巴细胞具有趋化性。最近的研究表明，IL-8是血管生成和诱导内皮细胞的增殖和趋化性。本研究旨在了解IL-8是否也对血管平滑肌细胞具有促有丝分裂和趋化作用。IL-8诱导的浓度依赖性（0.1至10 nmol/L）刺激DNA合成和细胞增殖的人和大鼠主动脉平滑肌细胞。此外，IL-8刺激平滑肌细胞产生前列腺素E（2），可抑制IL-8诱导的平滑肌细胞增殖。在存在吲哚美辛（5 μ mol/L）的情况下，IL-8（1 nmol/L）在孵育3天期间分别刺激人和大鼠主动脉平滑肌细胞数量增加61+/-16%和59+/-7%（n=4）。IL-8还使人和大鼠主动脉平滑肌细胞的DNA合成分别增加98+/-10%和151+/-27%（n=5）。此外，IL-8刺激大鼠主动脉平滑肌细胞迁移的20倍以上的控制值，EC（50）值为0.83 nmol/L，IL-8的这种趋化活性也被加强吲哚美辛。平滑肌细胞暴露于IL-8引起即刻早期基因c-fos和zif 268 mRNA的快速和瞬时表达。人和大鼠主动脉平滑肌细胞中c-fos和zif 268 mRNA的最高水平分别在IL-8刺激后30分钟和1小时观察到，随后迅速下降。此外，IL-8刺激平滑肌鳗鱼中的丝裂原活化蛋白（MAP）激酶，在刺激后5至10分钟达到峰值。在1和10 nmol/L IL-8，MAP激酶活性增加1.5和7倍以上的基础水平，分别。由于血管平滑肌细胞增殖和迁移是再狭窄和动脉粥样硬化中新生内膜形成的关键步骤，这些结果表明IL-8可能是血管平滑肌细胞的重要的天然有丝分裂原和化学引诱物，并可能在动脉内膜增厚和动脉粥样硬化的发病机制中发挥作用。
Interleukin-8 (IL-8) is a chemokine produced by a variety of cell types involved in atherogenesis and is chemotactic for neutrophils and lymphocytes. A recent study has shown that IL-8 is angiogenic and induces proliferation and chemotaxis of endothelial cells. The present study was undertaken to find out whether IL-8 is also mitogenic and chemotactic for vascular smooth muscle cells. IL-8 induced a concentration-dependent (0.1 to 10 nmol/L) stimulation of DNA synthesis and cell proliferation in both human and rat aortic smooth muscle cells. In addition, IL-8 stimulated smooth muscle cells to produce prostaglandin E(2), which can inhibit IL-8-induced smooth muscle cell proliferation. In the presence of indomethacin (5 mu mol/L), IL-8 (1 nmol/L) stimulated an increase in human and rat aortic smooth muscle cell number during a 3-day period of incubation by 61+/-16% and 59+/-7% (n=4), respectively. IL-8 also increased DNA synthesis in human and rat aortic smooth muscle cells by 98+/-10% and 151+/-27% (n=5), respectively. Moreover, IL-8 stimulated rat aortic smooth muscle cell migration by 20-fold over the control value, with an EC(50) value of 0.83 nmol/L; this chemotactic activity of IL-8 was also potentiated by indomethacin. Exposure of smooth muscle cells to IL-8 caused rapid and transient expression of the immediate-early genes c-fos and zif268 mRNA. The maximal levels of c-fos and zif268 mRNA in human and rat aortic smooth muscle cells were observed 30 minutes and 1 hour after stimulation with IL-8, respectively, followed by rapid decline. Moreover, IL-8 stimulated mitogen activated protein (MAP) kinase in smooth muscle eels with a peak at 5 to 10 minutes after stimulation. At 1 and 10 nmol/L IL-8, MAP kinase activity increased by 1.5- and 7-fold above the basal level, respectively. Since vascular smooth muscle cell proliferation and migration are crucial steps in neointimal formation in restenosis and atherosclerosis, these results suggest that IL-8 may be an important naturally occurring mitogen and chemoattractant for vascular smooth muscle cells and may play a role in the pathogenesis of arterial intimal thickening and atherosclerosis.