Influence of Age, Past Smoking, and Disease Severity on TLR2, Neutrophilic Inflammation, and MMP-9 Levels in COPD
Chronic obstructive pulmonary disease (COPD) is a common and serious respiratory disease, particularly in older individuals, characterised by fixed airway obstruction and persistent airway neutrophilia. The mechanisms that lead to these features are not well established. We investigated the contribu...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/462934 |
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| author | Jodie L. Simpson Vanessa M. McDonald Katherine J. Baines Kevin M. Oreo Fang Wang Philip M. Hansbro Peter G. Gibson |
| author_facet | Jodie L. Simpson Vanessa M. McDonald Katherine J. Baines Kevin M. Oreo Fang Wang Philip M. Hansbro Peter G. Gibson |
| author_sort | Jodie L. Simpson |
| collection | DOAJ |
| description | Chronic obstructive pulmonary disease (COPD) is a common and serious respiratory disease, particularly in older individuals, characterised by fixed airway obstruction and persistent airway neutrophilia. The mechanisms that lead to these features are not well established. We investigated the contribution of age, prior smoking, and fixed airflow obstruction on sputum neutrophils, TLR2 expression, and markers of neutrophilic inflammation. Induced sputum from adults with COPD () and healthy controls () was examined. A sputum portion was dispersed, total, differential cell count and viability recorded, and supernatant assayed for CXCL8, matrix metalloproteinase- (MMP-) 9, neutrophil elastase, and soluble TLR2. Peripheral blood cells () were stimulated and TLR2 activation examined. TLR2 levels were increased with ageing, while sputum neutrophils and total sputum MMP-9 levels increased with age, previous smoking, and COPD. In multivariate regression, TLR2 gene expression and MMP-9 levels were significant independent contributors to the proportion of sputum neutrophils after adjustment for age, prior smoking, and the presence of airflow obstruction. TLR2 stimulation led to enhanced release of MMP-9 from peripheral blood granulocytes. TLR2 stimulation activates neutrophils for MMP-9 release. Efforts to understand the mechanisms of TLR2 signalling and subsequent MMP-9 production in COPD may assist in understanding neutrophilic inflammation in COPD. |
| format | Article |
| id | doaj-art-f1ef529e39b84507b0c87f4befccaf71 |
| institution | DOAJ |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-f1ef529e39b84507b0c87f4befccaf712025-08-20T03:20:46ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/462934462934Influence of Age, Past Smoking, and Disease Severity on TLR2, Neutrophilic Inflammation, and MMP-9 Levels in COPDJodie L. Simpson0Vanessa M. McDonald1Katherine J. Baines2Kevin M. Oreo3Fang Wang4Philip M. Hansbro5Peter G. Gibson6NHMRC Centre for Respiratory and Sleep Medicine, Faculty of Health, School of Medicine and Public Health, The University of Newcastle, Callaghan, NSW 2308, AustraliaNHMRC Centre for Respiratory and Sleep Medicine, Faculty of Health, School of Medicine and Public Health, The University of Newcastle, Callaghan, NSW 2308, AustraliaNHMRC Centre for Respiratory and Sleep Medicine, Faculty of Health, School of Medicine and Public Health, The University of Newcastle, Callaghan, NSW 2308, AustraliaNHMRC Centre for Respiratory and Sleep Medicine, Faculty of Health, School of Medicine and Public Health, The University of Newcastle, Callaghan, NSW 2308, AustraliaNorman Bethune Medical College, Ji Lin University, Changchun 130021, ChinaPriority Research Centre for Asthma and Respiratory Diseases and Hunter Medical Research Institute, The University of Newcastle, Callaghan, NSW 2308, AustraliaNHMRC Centre for Respiratory and Sleep Medicine, Faculty of Health, School of Medicine and Public Health, The University of Newcastle, Callaghan, NSW 2308, AustraliaChronic obstructive pulmonary disease (COPD) is a common and serious respiratory disease, particularly in older individuals, characterised by fixed airway obstruction and persistent airway neutrophilia. The mechanisms that lead to these features are not well established. We investigated the contribution of age, prior smoking, and fixed airflow obstruction on sputum neutrophils, TLR2 expression, and markers of neutrophilic inflammation. Induced sputum from adults with COPD () and healthy controls () was examined. A sputum portion was dispersed, total, differential cell count and viability recorded, and supernatant assayed for CXCL8, matrix metalloproteinase- (MMP-) 9, neutrophil elastase, and soluble TLR2. Peripheral blood cells () were stimulated and TLR2 activation examined. TLR2 levels were increased with ageing, while sputum neutrophils and total sputum MMP-9 levels increased with age, previous smoking, and COPD. In multivariate regression, TLR2 gene expression and MMP-9 levels were significant independent contributors to the proportion of sputum neutrophils after adjustment for age, prior smoking, and the presence of airflow obstruction. TLR2 stimulation led to enhanced release of MMP-9 from peripheral blood granulocytes. TLR2 stimulation activates neutrophils for MMP-9 release. Efforts to understand the mechanisms of TLR2 signalling and subsequent MMP-9 production in COPD may assist in understanding neutrophilic inflammation in COPD.http://dx.doi.org/10.1155/2013/462934 |
| spellingShingle | Jodie L. Simpson Vanessa M. McDonald Katherine J. Baines Kevin M. Oreo Fang Wang Philip M. Hansbro Peter G. Gibson Influence of Age, Past Smoking, and Disease Severity on TLR2, Neutrophilic Inflammation, and MMP-9 Levels in COPD Mediators of Inflammation |
| title | Influence of Age, Past Smoking, and Disease Severity on TLR2, Neutrophilic Inflammation, and MMP-9 Levels in COPD |
| title_full | Influence of Age, Past Smoking, and Disease Severity on TLR2, Neutrophilic Inflammation, and MMP-9 Levels in COPD |
| title_fullStr | Influence of Age, Past Smoking, and Disease Severity on TLR2, Neutrophilic Inflammation, and MMP-9 Levels in COPD |
| title_full_unstemmed | Influence of Age, Past Smoking, and Disease Severity on TLR2, Neutrophilic Inflammation, and MMP-9 Levels in COPD |
| title_short | Influence of Age, Past Smoking, and Disease Severity on TLR2, Neutrophilic Inflammation, and MMP-9 Levels in COPD |
| title_sort | influence of age past smoking and disease severity on tlr2 neutrophilic inflammation and mmp 9 levels in copd |
| url | http://dx.doi.org/10.1155/2013/462934 |
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