Glucocorticoid sensitivity of lipopolysaccharide-stimulated chronic obstructive pulmonary disease alveolar macrophages
Glucocorticoid sensitivity of lipopolysaccharide-stimulated chronic obstructive pulmonary disease alveolar macrophages
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DOI：
10.1111/j.1365-2249.2009.03986.x
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发表时间：
2009-10-01
影响因子：
4.6
通讯作者：
Singh, D.
中科院分区：
文献类型：
--
作者：
Armstrong, J.;Sargent, C.;Singh, D.
有报道慢性阻塞性肺疾病（COPD）患者肺泡巨噬细胞对糖皮质激素（Gc）有抵抗作用。COPD巨噬细胞释放的炎症介质的Gc敏感性可能不同。本研究的目的是鉴定脂多糖（LPS）刺激COPD患者肺泡巨噬细胞产生的GC不敏感性炎症介质。来自15名COPD患者、9名吸烟者（S）和9名健康非吸烟者（HNS）的LPS刺激的肺泡巨噬细胞用LPS刺激，有或没有地塞米松（100和1000 nM）。采用Luminex和酶联免疫吸附法测定23种炎症介质。LPS刺激后，COPD患者和S组的炎症介质水平低于HNS组。两组间地塞米松在任一浓度下的作用均无差异（所有比较的P > 0，中心点05）。COPD患者中肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6和生长相关癌基因（GRO）-α对地塞米松的敏感性最高，而IL-8、粒细胞-巨噬细胞集落刺激因子（GM-CSF）和粒细胞集落刺激因子（G-CSF）的敏感性最低。COPD巨噬细胞对LPS的反应降低。与对照组相比，COPD巨噬细胞的GC敏感性相似。我们鉴定了一些Gc不敏感的细胞因子，包括GM-CSF、G-CSF和IL-8，它们可能参与COPD患者气道炎症的进展。
P>It has been reported that alveolar macrophages from patients with chronic obstructive pulmonary disease (COPD) display glucocorticoid (Gc) resistance. The Gc sensitivity of inflammatory mediators released by COPD macrophages may vary. The objective of this study was to identify Gc-insensitive inflammatory mediators produced by lipopolysaccharide (LPS)-stimulated alveolar macrophages from COPD patients. LPS-stimulated alveolar macrophages from 15 COPD patients, nine smokers (S) and nine healthy non-smokers (HNS) were stimulated with LPS with or without dexamethasone (100 and 1000 nM). Luminex and enzyme-linked immunosorbent assay were used to measure 23 inflammatory mediators. After LPS stimulation there were lower levels of inflammatory mediators in COPD patients and S compared to HNS. There was no difference between groups for the effects of dexamethasone at either concentration (P > 0 center dot 05 for all comparisons). Tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and growth-related oncogene (GRO)-alpha displayed the greatest sensitivity to dexamethasone in COPD patients, while IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) were the least sensitive. COPD macrophages have a reduced response to LPS. Gc sensitivity was similar in COPD macrophages compared to controls. We identify some Gc-insensitive cytokines, including GM-CSF, G-CSF and IL-8, that may be involved in the progression of airway inflammation in COPD patients.