Increased levels of osteopontin in sputum supernatant in severe refractory asthma
ABSTRACT Osteopontin (OPN) is a glycoprotein that has been associated with inflammation and fibrosis. Severe refractory asthma (SRA) is characterised by an intense inflammatory and remodelling process. The aim of this study was to investigate the levels of OPN in sputum supernatants of patients with SRA, to compare them with milder forms of the disease and to investigate their possible association with mediators and cells involved in the inflammatory and remodelling process.
33 patients with SRA, 29 with moderate asthma, 21 with steroid-naïve asthma and 20 healthy subjects were studied. All subjects underwent lung function tests, bronchial hyper-responsiveness assessment and sputum induction for cell count identification and measurement of OPN, vascular endothelial growth factor, transforming growth factor beta1 (TGF-beta1), cysteinyl leukotrienes, interleukin 13 (IL-13), eosinophilic cationic protein (ECP) and IL-8 in sputum supernatants.
Median (IQR) OPN levels (pg/ml) were significantly higher in patients with SRA than in those with moderate asthma, steroid-naive asthma and healthy control subjects (1840 (1125-11000) vs 130 (100-210) vs 100 (67-130) vs 50 (42-70), respectively, p<0.001). Regression analysis showed a significant association between log OPN and sputum eosinophils, cysteinyl leukotrienes, IL-13, TGF-beta1 and ECP. TGF-beta1 represented the strongest association with OPN. The above associations were not observed in milder forms of the disease or in healthy subjects.
The results indicate that OPN levels are higher in SRA than in less severe forms of the disease. Moreover, OPN is associated with mediators involved in both the inflammatory and remodelling process such as TGF-beta1, IL-13 and cysteinyl leukotrienes only in SRA.
Full-textDOI: · Available from: Davina Simoes, Jun 02, 2015
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ABSTRACT: Adenosine activated mast cells have been long implicated in allergic asthma and studies in rodent mast cells have assigned the A3 adenosine receptor (A3R) a primary role in mediating adenosine responses. Here we analyzed the functional impact of A3R activation on genes that are implicated in tissue remodeling in severe asthma in the human mast cell line HMC-1 that shares similarities with lung derived human mast cells. Quantitative real time PCR demonstrated upregulation of IL6, IL8, VEGF, amphiregulin and osteopontin. Moreover, further upregulation of these genes was noted upon the addition of dexamethasone. Unexpectedly, activated A3R down regulated its own expression and knockdown of the receptor replicated the pattern of agonist induced gene upregulation. This study therefore identifies the human mast cell A3R as regulator of tissue remodeling gene expression in human mast cells and demonstrates a heretofore-unrecognized mode of feedback regulation that is exerted by this receptor. Copyright © 2015 Elsevier Ltd. All rights reserved.Molecular Immunology 01/2015; 65(1):25-33. DOI:10.1016/j.molimm.2014.12.015 · 3.00 Impact Factor
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ABSTRACT: ABSTRACT Osteopontin (OPN) is a phosphorylated acidic glycoprotein that can function both as an extracellular matrix molecule and a cytokine. Recently published data support that OPN is up-regulated in surgical lung tissue samples of COPD patients.The aim of this study was to determine the levels of OPN in sputum supernatants of COPD patients and to investigate possible associations with mediators and cells involved in the inflammatory and remodeling process, as well as with the extent of emphysema.Seventy-seven COPD patients and 40 healthy subjects (20 smokers) were studied. All subjects underwent lung function tests, sputum induction for cell count identification and OPN, TGF-β1, MMP-2, IL-8, LTB4 measurement in sputum supernatants. High resolution computed tomography (HRCT) of the chest was performed for quantification of emphysema.OPN levels (pg/ml) were significantly higher in COPD patients compared to healthy smokers and non-smokers [median (IQR) 1340 (601,6227) vs. 101(77,110) vs. 68 (50,89) respectively, p<0.001]. Regression analysis showed a significant association between OPN and sputum neutrophils, IL-8, MMP-2 and the extent of emphysema. The above associations were not observed in healthy subjects.OPN levels are higher in COPD patients compared to healthy subjects. OPN may play a role in the neutrophilic inflammation and in the pathogenesis of emphysema.Chest 06/2014; 146(4). DOI:10.1378/chest.13-2440 · 7.13 Impact Factor
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