title: Temporal changes in glutaredoxin 1 and protein s-glutathionylation in allergic airway inflammation.
abstract: BACKGROUND
  Asthma is a chronic inflammatory disorder of the airways, involving oxidative stress. Upon oxidative stress, glutathione covalently binds to protein thiols to protect them against irreversible oxidation. This posttranslational modification, known as protein S-glutathionylation, can be reversed by glutaredoxin 1 (Glrx1) under physiological condition. Glrx1 is known to increase in the lung tissues of a murine model of allergic airway inflammation. However, the temporal relationship between levels of Glrx1, protein S-glutathionylation, and glutathione in the lungs with allergic airway inflammation is not clearly understood.
  
  
  METHODS
  BALB/c mice received 3 aerosol challenges with ovalbumin (OVA) following sensitization to OVA. They were sacrificed at 6, 24, 48, or 72 h, or 8 days (5 mice per group), and the levels of Glrx1, protein S-glutathionylation, glutathione, and 25 cytokines/chemokines were evaluated in bronchoalveolar lavage fluid (BALF) and/or lung tissue.
  
  
  RESULTS
  Levels of Glrx1 in BALF were significantly elevated in the OVA 6 h (final challenge) group compared to those in the control, with concurrent increases in protein S-glutathionylation levels in the lungs, as well as total glutathione (reduced and oxidized) and oxidized glutathione in BALF. Protein S-glutathionylation levels were attenuated at 24 h, with significant increases in Glrx1 levels in lung tissues at 48 and 72 h. Glrx1 in alveolar macrophages was induced after 6 h. Glrx1 levels concomitantly increased with Th2/NF-κB-related cytokines and chemokines in BALF.
  
  
  CONCLUSIONS
  The temporal relationships of Glrx1 with protein S-glutathionylation, glutathione, and cytokines/chemokines were observed as dynamic changes in lungs with allergic airway inflammation, suggesting that Glrx1 and protein-SSG redox status may play important roles in the development of allergic airway inflammation.
authors: First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
authors: Kanako
authors: K
authors: Maki
authors: First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
authors: Katsura
authors: K
authors: Nagai
authors: First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
authors: Masaru
authors: M
authors: Suzuki
authors: First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
authors: Takashi
authors: T
authors: Inomata
authors: First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
authors: Takayuki
authors: T
authors: Yoshida
authors: First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
authors: Masaharu
authors: M
authors: Nishimura
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D054477:Glutaredoxins / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018384:Oxidative Stress
chemical_list: D016207:Cytokines; D054477:Glutaredoxins; D005978:Glutathione