Sputum biomarkers in IPF: Evidence for raised gene expression and protein level of IGFBP-2, IL-8 and MMP-7

• Published in: PloS one Vol. 12; no. 2; p. e0171344
• Main Authors: Guiot, J., Henket, M., Corhay, J. L., Moermans, C., Louis, R.
• Format: Journal Article Web Resource
• Language: English
• Published: United States Public Library of Science 08.02.2017; Public Library of Science (PLoS)
• Subjects: Ambulatory care; Biological markers; Biology and Life Sciences; Biomarkers; Cardiovascular & respiratory systems; Chronic obstructive pulmonary disease; Cross-Sectional Studies; Cytokines; Diagnosis; Eosinophils; Epithelial cells; Female; Fibrosis; Gelatinase B; Gene Expression; Genetic aspects; Human health sciences; Humans; Idiopathic Pulmonary Fibrosis - diagnosis; Idiopathic Pulmonary Fibrosis - genetics; Idiopathic Pulmonary Fibrosis - metabolism; Inflammation; Insulin-Like Growth Factor Binding Protein 2 - genetics; Insulin-Like Growth Factor Binding Protein 2 - metabolism; Insulin-like growth factor I; Insulin-like growth factor-binding protein 1; Insulin-like growth factor-binding protein 2; Insulin-like growth factor-binding protein 3; Insulin-like growth factors; Interleukin 13; Interleukin 6; Interleukin 8; Interleukin-8 - genetics; Interleukin-8 - metabolism; IPF; Kinases; Leukocyte Count; Leukocytes (eosinophilic); Leukocytes (neutrophilic); Lung diseases; Macrophages; Male; Matrilysin; Matrix Metalloproteinase 7 - genetics; Matrix Metalloproteinase 7 - metabolism; Medicine and Health Sciences; Patients; Proteins; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - metabolism; Pulmonary fibrosis; Research and Analysis Methods; Respiratory Function Tests; Respiratory tract; Respiratory tract diseases; Sarcoidosis; Sciences de la santé humaine; Sputum; Sputum - cytology; Sputum - metabolism; Surfactants; Systèmes cardiovasculaire & respiratoire; Tumor necrosis factor-α
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0171344

Idiopathic pulmonary fibrosis (IPF) is a rare lung disease of unknown origin leading rapidly to death. This paper addresses the issue of whether sputum induction is a suitable tool to study respiratory tract inflammation and potential biomarkers in IPF compared to COPD, a fibrosing airway wall disease. In a cross-sectional analysis, 15 IPF patients, 32 COPD and 30 healthy subjects underwent sputum induction. Total sputum cell counts and the amount of TGF- β, IGF-1, IGF-2, IGFBP-1, IGFBP-2, IGFBP-3, IL-8, IL-13, MMP-7, MMP-9, YKL-40, TNF-α and KL-6 in sputum supernatant were analysed. We also profiled gene expression of cells in the induced sputum for TGF-β, MMP-7, YKL-40, IGFBP-2, IL-6, IL-8 and TNF-α. IPF patients, like COPD, had increased sputum absolute number of neutrophils, eosinophils, macrophages and epithelial cells compared to HS. IPF sputum supernatants had increased concentrations of IGFBP-2, IL-8, TGF-β, MMP-7, MMP-9 and KL-6 (p<0.05, p<0.0001, p<0.05, p<0.05, p<0.0001, p<0.05 respectively) when compared to healthy subjects where COPD had higher IL-6 and TNF-α levels than IPF (p<0.05 and p<0.05 respectively) and HS (p<0.0001 and p<0.001 respectively) and higher IL-8 and MMP-9 than HS (p<0.0001 and p<0.001 respectively). Conversely to IL-6 and TNF-α, MMP-7 was increased in IPF compared to COPD (p<0.05). The KL-6 and MMP-7 protein levels in sputum were inversely correlated with total lung capacity (TLC, % of predicted) in IPF patients (r = -0.73 and r = -0.53 respectively). Sputum gene expression analysis identified a significant increase for IGFBP-2, IL-6, IL-8 and MMP-7 in IPF compared to HS (p<0.05, p<0.01, p<0.05 and p<0.0001 respectively) and for IGFBP-2, YKL-40, IL-6, IL-8 and MMP-7 compared to COPD (p<0.01, p<0.01, p<0.05, p<0.01 and p<0.0001 respectively). Furthermore, gene expression of TGF-β was increased in IPF compared to COPD (p<0.001) but not to HS. Our data show clear increase in expression and production of IGFBP-2, IL-8 and MMP-7 in sputum from patients with IPF that may contribute to the disease.