Interleukin-8: novel roles in human airway smooth muscle cell contraction and migration
Interleukin-8: novel roles in human airway smooth muscle cell contraction and migration
复制标题
DOI：
10.1152/ajpcell.00451.2005
复制
发表时间：
2006-11-01
影响因子：
5.5
通讯作者：
Martin, James G.
中科院分区：
文献类型：
--
作者：
Govindaraju, Vasanthi;Michoud, Marie-Claire;Martin, James G.
在囊性纤维化（CF）和哮喘患者中，气道中发现白细胞介素-8（IL-8）水平升高。IL-8是一种CXC趋化因子，是通过CXCR 1和CXCR 2 G蛋白偶联受体对中性粒细胞的化学引诱物。我们假设IL-8直接作用于气道平滑肌细胞（ASMC），可能有助于CF和哮喘中观察到的气道反应性增强和气道重塑。本研究的目的是确定人ASMC（HASMC）是否表达与细胞收缩和迁移相关的功能性IL-8受体（CXCR 1和CXCR 2）。实验在从人肺标本收获的细胞上进行。实时荧光定量PCR和荧光激活细胞分选分析显示，HASMC表达CXCR 1和CXCR 2的mRNA和蛋白。细胞内Ca 2+浓度（[Ca 2 +]（i））响应于IL-8（100 nM）从115增加到170 nM，并在用U-73122抑制磷脂酶C（PLC）后降低。用特异性中和抗体阻断受体后，[Ca 2 +]（i）的变化被消除。IL-8还收缩HASMC，使细胞长度减少15%，并诱导迁移增加2.5倍。这些结果表明，HASMC组成型表达功能性CXCR 1和CXCR 2，介导IL-8触发的Ca 2+释放，收缩和迁移。这些数据表明IL-8在引起哮喘和CF的气道结构和功能异常中的潜在作用。
In patients with cystic fibrosis (CF) and asthma, elevated levels of interleukin-8 (IL-8) are found in the airways. IL-8 is a CXC chemokine that is a chemoattractant for neutrophils through CXCR1 and CXCR2 G protein-coupled receptors. We hypothesized that IL-8 acts directly on airway smooth muscle cells (ASMC) in a way that may contribute to the enhanced airway responsiveness and airway remodeling observed in CF and asthma. The aim of this study was to determine whether human ASMC (HASMC) express functional IL-8 receptors (CXCR1 and CXCR2) linked to cell contraction and migration. Experiments were conducted on cells harvested from human lung specimens. Real-time PCR and fluorescence-activated cell sorting analysis showed that HASMC expressed mRNA and protein for both CXCR1 and CXCR2. Intracellular Ca2+ concentration ([Ca2+](i)) increased from 115 to 170 nM in response to IL-8 (100 nM) and decreased after inhibition of phospholipase C (PLC) with U-73122. On blocking the receptors with specific neutralizing antibodies, changes in [Ca2+](i) were abrogated. IL-8 also contracted the HASMC, decreasing the length of cells by 15%, and induced a 2.5-fold increase in migration. These results indicate that HASMC constitutively express functional CXCR1 and CXCR2 that mediate IL-8-triggered Ca2+ release, contraction, and migration. These data suggest a potential role for IL-8 in causing abnormal airway structure and function in asthma and CF.