期刊
RESPIRATION
卷 81, 期 6, 页码 499-510出版社
KARGER
DOI: 10.1159/000324297
关键词
Alveolar macrophages; Chronic obstructive pulmonary disease; Disease-specific genes; FEV1; Lung function; Microarray; Monocytes
资金
- Wellcome Trust
- National Office for Research and Technology [NKFP 1/007/01, 1A/008/04]
- Hungarian Scientific Research Fund [NI 67877]
Background: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by progressive airflow limitation and significant extrapulmonary (systemic) effects that lead to co-morbid conditions, though the pathomechanism of COPD is largely undetermined. Alveolar macrophages (AM) derived from peripheral monocytes (MO) appear to play a key role in initiating and/or sustaining disease progression. Objectives: To identify disease-and cell type-specific gene expression profiles and potential overlaps in those in order to diagnose COPD, characterize its progression and determine the effect of drug treatment. Method: Global gene expression analysis was used for primary screening in order to obtain expression signatures of AMs and circulating MOs of COPD patients and healthy controls. The results of microarray analyses of AMs (20 controls and 26 COPD patients) and MOs (16 controls and 22 COPD patients) were confirmed and validated by realtime quantitative polymerase chain reaction. Results: We have identified gene sets specifically associated with COPD in AMs and MOs. There were overlapping genes between the two cell types. Our data also show that COPD-specific gene expression signatures in AMs and MOs correlate with percent of predicted FEV1. Conclusion: Disease-specific and overlapping gene expression signatures can be defined in lung-derived macrophages and also in circulating monocytes. Some of the validated expression changes in both cell types correlate with lung function and therefore could serve as biomarkers of disease progression. Copyright (C) 2011 S. Karger AG, Basel
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