[en] Alterations in glutathione and its metabolism contribute to oxidative stress in COPD, but the role of S-glutathionylation (PSSG) and its major regulator glutaredoxin 1 (Grx1) remains unclear. This study investigated the Grx1/PSSG axis in sputum of COPD patients and its associations with lung function and inflammation, as well as Grx1 secretion in mouse models and in cell culture. In patients with an acute exacerbation, PSSG levels were significantly decreased in sputum, while Grx1 protein and total Grx activity were increased compared to stable COPD. No differences were observed between healthy smokers and stable patients. PSSG levels correlated negatively with sputum neutrophils, IL-8 and IL-1β, but positively with lung function parameters, whereas Grx1 showed the opposite pattern. Enhanced Grx1 levels were also detected in bronchoalveolar lavage fluid from mice exposed to cigarette smoke or chronic pulmonary inflammation. Moreover, epithelial cells and macrophages secreted Grx1 in response to pro-inflammatory mediators, and Grx1 modulated expression of MMPs by macrophages in vitro and in vivo. In conclusion, this study identifies the Grx1/PSSG redox axis as a potential important factor in COPD pathogenesis, especially during exacerbations. Further research should examine in more detail the intricate relation of extracellular Grx1 with lung function and inflammation.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Kuipers, Ine; Department of Respiratory Medicine, Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands.
Krijgsman, Renske; Department of Respiratory Medicine, Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands.
Louis, Renaud ; Université de Liège - ULiège > Département des sciences cliniques > Pneumologie - Allergologie
Corhay, Jean-Louis ; Université de Liège - ULiège > Département des sciences de la santé publique
Azevedo Mendes, Thibault-Marie ; Centre Hospitalier Universitaire de Liège - CHU > > Frais communs médecine - Pool assistants
Brusselle, Guy G; Department of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium.
Bracke, Ken R ; Department of Respiratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium.
Reynaert, Niki L; Department of Respiratory Medicine, Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands.
Language :
English
Title :
Sputum Glutaredoxin 1 and Protein S-Glutathionylation in COPD.
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