Blog
About

14
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Matrix metalloproteinases -8, -9 and -12 in smokers and patients with Stage 0 COPD

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          COPD is underdiagnosed and its early assessment is problematic. It has been suggested that symptomatic smokers with normal FEV 1/FVC (Stage 0 COPD, GOLD criteria) can develop COPD in the future. Potential early biomarkers in COPD include the matrix metallo-proteinases (MMPs). It is not yet known, whether alterations in MMP expression are associated with smoking alone or with the risk of developing COPD. In this cross-sectional study MMP-8, MMP-9 and MMP-12 were determined from induced sputum and plasma by ELISA, immunocytochemistry, zymography, and/or Western blot in non-smokers (n = 32), smokers with symptoms (Stage 0, GOLD criteria) (n = 23) or without symptoms (n = 23). Only MMP-8 differentiated Stage 0 COPD from non-symptomatic smokers (p = 0.02). MMP-9 levels were significantly elevated in the induced sputum of non-symptomatic smokers and Stage 0 COPD (p = 0.01, p < 0.001) compared to non-smokers, but did not differ between the two subgroups of smokers. MMP-12 was higher only at Stage 0 compared to non-smokers (p = 0.04). MMP-8, MMP-9 and MMP-12 immunoreactivity was localized in macrophages and neutrophils, especially in smokers. MMP-8 levels correlated significantly with the small airway flow parameters (MEF50, MEF25) (p = 0.005 and p = 0.0004) and markers of neutrophil activation (myeloperoxidase, lactoferrin). In conclusion MMP-8 may differentiate Stage 0 from healthy smokers.

          Related collections

          Most cited references 48

          • Record: found
          • Abstract: not found
          • Article: not found

          Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary.

           ,  Suzanne Hurd,  P Calverley (2001)
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Chronic obstructive pulmonary disease: molecular and cellular mechanisms.

            Chronic obstructive pulmonary disease is a leading cause of death and disability, but has only recently been extensively explored from a cellular and molecular perspective. There is a chronic inflammation that leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This is characterised by increased numbers of alveolar macrophages, neutrophils and cytotoxic T-lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). A high level of oxidative stress may amplify this inflammation. There is also increased elastolysis and evidence for involvement of several elastolytic enzymes, including serine proteases, cathepsins and matrix metalloproteinases. The inflammation and proteolysis in chronic obstructive pulmonary disease is an amplification of the normal inflammatory response to cigarette smoke. This inflammation, in marked contrast to asthma, appears to be resistant to corticosteroids, prompting a search for novel anti-inflammatory therapies that may prevent the relentless progression of the disease.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Oxidative stress and redox regulation of lung inflammation in COPD.

               I Rahman,  I. Adcock (2006)
              Reactive oxygen species, either directly or via the formation of lipid peroxidation products, may play a role in enhancing inflammation through the activation of stress kinases (c-Jun activated kinase, extracellular signal-regulated kinase, p38) and redox-sensitive transcription factors, such as nuclear factor (NF)-kappaB and activator protein-1. This results in increased expression of a battery of distinct pro-inflammatory mediators. Oxidative stress activates NF-kappaB-mediated transcription of pro-inflammatory mediators either through activation of its activating inhibitor of kappaB-alpha kinase or the enhanced recruitment and activation of transcriptional co-activators. Enhanced NF-kappaB-co-activator complex formation results in targeted increases in histone modifications, such as acetylation leading to inflammatory gene expression. Emerging evidence suggests the glutathione redox couple may entail dynamic regulation of protein function by reversible disulphide bond formation on kinases, phosphatases and transcription factors. Oxidative stress also inhibits histone deacetylase activity and in doing so further enhances inflammatory gene expression and may attenuate glucocorticoid sensitivity. The antioxidant/anti-inflammatory effects of thiol molecules (glutathione, N-acetyl-L-cysteine and N-acystelyn, erdosteine), dietary polyphenols (curcumin-diferuloylmethane, cathechins/quercetin and reserveratol), specific spin traps, such as alpha-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (extracellular superoxide dismutase (SOD) mimetic, SOD mimetic M40419 and SOD, and catalase manganic salen compound, eukarion-8), porphyrins (AEOL 10150 and AEOL 10113) and theophylline have all been shown to play a role in either controlling NF-kappaB activation or affecting histone modifications with subsequent effects on inflammatory gene expression in lung epithelial cells. Thus, oxidative stress regulates both key signal transduction pathways and histone modifications involved in lung inflammation. Various approaches to enhance lung antioxidant capacity and clinical trials of antioxidant compounds in chronic obstructive pulmonary disease are also discussed.
                Bookmark

                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                September 2007
                September 2007
                : 2
                : 3
                : 369-379
                Affiliations
                [1 ]Department of Medicine and Divisions of Pulmonary Medicine and
                [2 ]Allergology,
                [3 ]Departments of Clinical Physiology and
                [4 ]Oral and Maxillofacial Diseases, University of Helsinki, Biomedicum Helsinki and Helsinki University Central Hospital, Helsinki, Finland
                [5 ]Department of Respiratory Diseases, Ghent University Hospital, Ghent, Belgium
                Author notes
                Correspondence: Vuokko L Kinnula, University of Helsinki, Department of Medicine, PO Box 22, 00014 Helsinki, Finland, Tel 358 9 4717 2255, Fax 358 9 4717 6107, Email vuokko.kinnula@ 123456helsinki.fi
                Article
                copd-2-369
                2695187
                18229576
                © 2007 Dove Medical Press Limited. All rights reserved
                Categories
                Original Research

                Respiratory medicine

                myeloperoxidase, gold, mmp, oxidant, copd, cigarette smoking, stage 0

                Comments

                Comment on this article