Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Shapingba, Chongqing, China Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia.
Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia Discipline of Pharmacology, The University of Sydney, Sydney, NSW, Australia.
Eur Respir J. 2014 Sep;44(3):634-46. doi: 10.1183/09031936.00171313. Epub 2014 Jun 25.
We hypothesised that the response to cigarette smoke in airway smooth muscle (ASM) cells from smokers with chronic obstructive pulmonary disease (COPD) would be intrinsically different from smokers without COPD, producing greater pro-inflammatory mediators and factors relating to airway remodelling. ASM cells were obtained from smokers with or without COPD, and then stimulated with cigarette smoke extract (CSE) or transforming growth factor-β1. The production of chemokines and matrix metalloproteinases (MMPs) were measured by ELISA, and the deposition of collagens by extracellular matrix ELISA. The effects of CSE on cell attachment and wound healing were measured by toluidine blue attachment and cell tracker green wound healing assays. CSE increased the release of CXCL8 and CXCL1 from human ASM cells, and cells from smokers with COPD produced more CSE-induced CXCL1. The production of MMP-1, -3 and -10, and the deposition of collagen VIII alpha 1 (COL8A1) were increased by CSE, especially in the COPD group which had higher production of MMP-1 and deposition of COL8A1. CSE decreased ASM cell attachment and wound healing in the COPD group only. ASM cells from smokers with COPD were more sensitive to CSE stimulation, which may explain, in part, why some smokers develop COPD.
我们假设，患有慢性阻塞性肺疾病（COPD）的吸烟者的气道平滑肌（ASM）细胞对香烟烟雾的反应与没有 COPD 的吸烟者内在不同，会产生更多的促炎介质和与气道重塑相关的因子。我们从有或没有 COPD 的吸烟者中获取 ASM 细胞，然后用香烟烟雾提取物（CSE）或转化生长因子-β1 刺激它们。通过 ELISA 测量趋化因子和基质金属蛋白酶（MMPs）的产生，通过细胞外基质 ELISA 测量胶原蛋白的沉积。通过甲苯胺蓝附着和细胞追踪绿色伤口愈合测定来测量 CSE 对细胞附着和伤口愈合的影响。CSE 增加了人 ASM 细胞中 CXCL8 和 CXCL1 的释放，并且来自 COPD 吸烟者的细胞产生了更多的 CSE 诱导的 CXCL1。CSE 增加了 MMP-1、MMP-3 和 MMP-10 的产生以及 COL8A1 的沉积，尤其是在 COPD 组中，MMP-1 的产生和 COL8A1 的沉积更高。CSE 仅降低 COPD 组中 ASM 细胞的附着和伤口愈合。来自 COPD 吸烟者的 ASM 细胞对 CSE 刺激更为敏感，这部分解释了为什么有些吸烟者会发展为 COPD。
