Pro-inflammatory phenotype of COPD fibroblasts not compatible with repair in COPD lung.
Pro-inflammatory phenotype of COPD fibroblasts not compatible with repair in COPD lung.
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COPD 成纤维细胞的促炎表型与 COPD 肺的修复不相容
DOI：
10.1111/j.1582-4934.2011.01492.x
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发表时间：
2012-07
影响因子：
5.3
通讯作者：
Black PN
中科院分区：
文献类型：
--
作者：
Zhang J;Wu L;Qu JM;Bai CX;Merrilees MJ;Black PN
慢性阻塞性肺疾病（COPD）的特征在于小气道和肺泡壁的弹性纤维的损失，其中弹性蛋白的减少随着疾病的严重程度而增加。目前还不清楚为什么缺乏弹性纤维的修复。我们已经检查了从患有或不患有COPD的受试者的肺组织培养的成纤维细胞，以确定分泌特征是否解释了组织修复的缺乏。在本研究中，从轻度COPD [慢性阻塞性肺疾病全球倡议（GOLD）1，n= 5]、中度至重度COPD（GOLD 2-3，n= 12）和对照（非COPD，n= 5）患者的肺实质中培养成纤维细胞。测量增殖、衰老相关β-半乳糖苷酶-1、IL-6、IL-8、MMP-1、弹性蛋白原和多功能蛋白聚糖的mRNA表达，以及IL-6、IL-8、PGE 2、弹性蛋白原、不溶性弹性蛋白和多功能蛋白聚糖的蛋白水平。GOLD 2-3成纤维细胞增殖较慢（P < 0.01），衰老相关β-半乳糖苷酶-1水平较高（P < 0.001），并显示IL-6的mRNA和/或蛋白质显著增加（P < 0.05）、IL-8（P < 0.01）、MMP-1（P < 0.05）、PGE 2（P <0.05）、多功能蛋白聚糖（P < 0.05）和弹性蛋白原（P < 0.05）。弹性蛋白原（P < 0.01）、多功能蛋白聚糖（P < 0.05）、IL-6（P <0.05）和IL-8（P < 0.05）的mRNA表达和/或蛋白水平与FEV1%预测值呈负相关。不溶性弹性蛋白没有增加。总之，来自中度至重度COPD受试者的成纤维细胞表现出分泌表型，炎症分子（包括基质蛋白聚糖多功能蛋白聚糖）上调，可溶性但非不溶性弹性蛋白增加。Versican抑制原弹性蛋白组装成不溶性弹性蛋白，我们得出结论，COPD成纤维细胞的促炎表型与弹性纤维的修复不相容。
Chronic obstructive pulmonary disease (COPD) is characterized by loss of elastic fibres from small airways and alveolar walls, with the decrease in elastin increasing with disease severity. It is unclear why there is a lack of repair of elastic fibres. We have examined fibroblasts cultured from lung tissue from subjects with or without COPD to determine if the secretory profile explains lack of tissue repair. In this study, fibroblasts were cultured from lung parenchyma of patients with mild COPD [Global initiative for chronic Obstructive Lung Disease (GOLD) 1, n= 5], moderate to severe COPD (GOLD 2–3, n= 12) and controls (non‐COPD, n= 5). Measurements were made of proliferation, senescence‐associated β‐galactosidase‐1, mRNA expression of IL‐6, IL‐8, MMP‐1, tropoelastin and versican, and protein levels for IL‐6, IL‐8, PGE2, tropoelastin, insoluble elastin, and versican. GOLD 2–3 fibroblasts proliferated more slowly (P < 0.01), had higher levels of senescence‐associated β‐galactosidase‐1 (P < 0.001) than controls and showed significant increases in mRNA and/or protein for IL‐6 (P < 0.05), IL‐8 (P < 0.01), MMP‐1 (P < 0.05), PGE2 (P < 0.05), versican (P < 0.05) and tropoelastin (P < 0.05). mRNA expression and/or protein levels of tropoelastin (P < 0.01), versican (P < 0.05), IL‐6 (P < 0.05) and IL‐8 (P < 0.05) were negatively correlated with FEV1% of predicted. Insoluble elastin was not increased. In summary, fibroblasts from moderate to severe COPD subjects display a secretory phenotype with up‐regulation of inflammatory molecules including the matrix proteoglycan versican, and increased soluble, but not insoluble, elastin. Versican inhibits assembly of tropoelastin into insoluble elastin and we conclude that the pro‐inflammatory phenotype of COPD fibroblasts is not compatible with repair of elastic fibres.
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影响因子：
2.7
作者：
Beikler T;Peters U;Prior K;Eisenacher M;Flemmig TF
通讯作者：
Flemmig TF
影响因子：
82.9
作者：
Fink, L;Seeger, W;Bohle, RM
通讯作者：
Bohle, RM
影响因子：
158.5
作者：
HOGG, JC;MACKLEM, PT;THURLBECK, WM
通讯作者：
THURLBECK, WM
影响因子：
14
作者：
Klapperich, CM;Bertozzi, CR
通讯作者：
Bertozzi, CR
影响因子：
9.8
作者：
Hinek, A;Smith, AC;Weksberg, R
通讯作者：
Weksberg, R