Human IL-8 regulates smooth muscle cell VCAM-1 expression in response to endothelial cells exposed to atheroprone flow.
Human IL-8 regulates smooth muscle cell VCAM-1 expression in response to endothelial cells exposed to atheroprone flow.
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DOI：
10.1161/atvbaha.109.184382
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发表时间：
2009-05
期刊：
影响因子：
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通讯作者：
Blackman BR
中科院分区：
文献类型：
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作者：
Hastings NE;Feaver RE;Lee MY;Wamhoff BR;Blackman BR
白细胞介素-8（IL-8）是一种可溶性的人类特异性趋化因子，与慢性炎症性疾病动脉粥样硬化的发展有关。最近，我们发现动脉粥样硬化酮血流动力学诱导IL-8分泌的内皮细胞（EC）同时增加EC/平滑肌细胞（SMC）VCAM-1的表达在人类血液动力学共培养模型。尽管IL-8与炎症相关，但我们在此表明，在动脉粥样硬化流动过程中阻断IL-8活性导致EC/SMC VCAM-1表达水平升高。我们检验了IL-8限制SMC VCAM-1表达以响应炎症刺激的假设，无论是动脉粥样硬化剂流动还是细胞因子白细胞介素-1 β（IL-1β）的加入。Atheroprone流量增加单核细胞粘附EC/SMC，同时诱导VCAM-1蛋白。VCAM-1抗血清减弱了这种反应。IL-1β使SMC中的VCAM-1上调3倍，这一反应在24小时时被添加IL-8抑制。IL-1β和IL-8均不诱导增殖或迁移。在IL-1β存在下，IL-8受体CXCR 2的中和进一步诱导VCAM-1，并且NF-κB活化和VCAM-1表达需要磷酸化p38。此外，IL-8降低单独IL-1β诱导的p38活化和NF-κB活性。总之，这些发现为IL-8通过VCAM-1调节限制EC/SMC中的炎症反应的新作用提供了证据。（Arterioscler Thromb Vasc Biol.2009;29：725-731.）
Interleukin-8 (IL-8) is a soluble human-specific chemokine implicated in the development of the chronic inflammatory disease atherosclerosis. Recently, we showed that atheroprone hemodynamics induced IL-8 secretion from endothelial cells (ECs) concurrent with increased EC/smooth muscle cell (SMC) VCAM-1 expression in a human hemodynamic coculture model. Despite an IL-8 association with inflammation, we show here that blocking IL-8 activity during atheroprone flow resulted in increased levels of EC/SMC VCAM-1 expression. We tested the hypothesis that IL-8 limits SMC VCAM-1 expression in response to inflammatory stimuli, either atheroprone flow or cytokine interleukin-1β (IL-1β) addition. Atheroprone flow increased monocyte adhesion in both EC/SMCs, concurrent with the induction of VCAM-1 protein. VCAM-1 antisera attenuated this response. IL-1β upregulated VCAM-1 in SMCs by 3-fold, a response inhibited by the addition of IL-8 at 24 hours. Neither IL-1β nor IL-8 induced proliferation or migration. Neutralization of the IL-8 receptor, CXCR2, further induced VCAM-1 in the presence of IL-1β, and phospho-p38 was required for NF-κB activation and VCAM-1 expression. Additionally, IL-8 reduced p38 activation and NF-κB activity induced by IL-1β alone. Together, these findings provide evidence for a novel role whereby IL-8 limits the inflammatory response in ECs/SMCs via VCAM-1 modulation. (Arterioscler Thromb Vasc Biol. 2009;29:725-731.)