Cigarette smoke extract induced cytokine and chemokine gene expression changes in COPD macrophages
Cigarette smoke extract induced cytokine and chemokine gene expression changes in COPD macrophages
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DOI：
10.1016/j.cyto.2008.02.001
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发表时间：
2008-05-01
期刊：
影响因子：
3.8
通讯作者：
Singh, Dave
中科院分区：
文献类型：
--
作者：
Kent, Lauren;Smyth, Lucy;Singh, Dave
巨噬细胞是慢性阻塞性肺疾病（COPD）中的关键炎症细胞。COPD巨噬细胞中香烟烟雾（CS）对炎症信号通路的转录调节尚未完全了解。我们研究了急性CS暴露对COPD巨噬细胞细胞因子、趋化因子和信号转导基因表达谱的影响。用1%、10%和25%的CS提取物（CSE）刺激来自COPD患者（n = 6）的全血的单核细胞衍生的巨噬细胞（MDM）6小时，用于微阵列和定量聚合酶链反应（Q-PCR）分析。我们观察到显著调节基因的数量呈CSE剂量依赖性增加;在1%、10%和25%CSE下分别有24、340和627个基因。IL-8 mRNA水平被10% CSE上调（2.25倍增加，95%CI 1.28-4.00）。相反，在10%和25% CSE下，一系列其他细胞因子和趋化因子下调，包括IL-1 β、IL-1 β-6、IL-1 β-10和IL-1 β-18、趋化因子配体CCL-2、CCL-3、CCL-4、CCL-5、CCL-8、CCL-15、CCL-20和CXCL-1、CXCL-2和CXCL-10。Q-PCR和微阵列数据高度相关（r = 0.95，p = 0.0001）。CSE抑制NF-κ B组分p50和I κ B α表达，而AP-1组分c-Jun、FOSL 1和FOSL 2上调。急性CSE暴露降低了巨噬细胞炎症基因表达，除了增加IL-8。关键炎症信号通路基因的调控存在多样性。急性CS暴露的影响似乎包括通过IL-8上调趋化机制，但也下调先天免疫。(C)2008爱思唯尔有限公司保留所有权利。
Macrophages are key inflammatory cells in chronic obstructive pulmonary disease (COPD). The transcriptional regulation of inflammatory signalling pathways by cigarette smoke (CS) in COPD macrophages is not well understood. We have studied the effects of acute CS exposure on COPD macrophage cytokine, chemokine and signal transduction gene expression profiles. Monocyte derived macrophages (MDMs) from whole blood from patients with COPD (n = 6) were stimulated with 1%, 10% and 25% CS extract (CSE) for 6 h for microarray and quantitative polymerase chain reaction (Q-PCR) analysis. We observed a CSE dose dependant increase in the numbers of significantly regulated genes; 24, 340 and 627 genes at 1%, 10% and 25% CSE, respectively. IL-8 mRNA levels were up-regulated by 10% CSE (2.25-fold increase, 95% CI 1.28-4.00). In contrast a range of other cytokines and chemokines were down-regulated at both 10% and 25% CSE, including IL-1 beta, -6, -10 and -18, chemokine ligands CCL-2,-3,-4,-5,-8, -15, -20 and CXCL-1, -2 and -10. Q-PCR and microarray data were highly correlated (r = 0.95, p = 0.000 1). NF-kappa B component p50 and I kappa B alpha expression were suppressed by CSE, while there was up-regulation of the AP-1 components c-Jun, FOSL1 and FOSL2. Acute CSE exposure decreased macrophage inflammatory gene expression, with the exception of increased IL-8. There was diverse regulation of key inflammatory signal pathway genes. The effects of acute CS exposure appear to encompass both up-regulation of chemotaxis mechanisms through IL-8, but also down-regulation of innate immunity. (C) 2008 Elsevier Ltd. All rights reserved.