TY - JOUR T1 - Compartment-specific overexpression of glutathione peroxidases during lung fibrosis JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P2022 AU - Claudia Staab-Weijnitz AU - Isis Fernandez AU - Herbert Schiller AU - Katharina Heinzelmann AU - Martina Sterclova AU - Martina Vasakova AU - Matthias Mann AU - Oliver Eickelberg Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P2022.abstract N2 - Rationale: Idiopathic pulmonary fibrosis (IPF) is associated with oxidative stress and depletion of the antioxidant glutathione (GSH) in epithelial lining fluid (ELF) and tissue. However, differential expression of GSH-metabolizing enzymes in bronchoalveolar lavage fluid (BALF) and tissue during lung fibrosis has not been comprehensively studied.Methods: In a label-free whole-proteome approach, we assessed levels of GSH-metabolizing enzymes in BALF and tissue during the onset and resolution of bleomycin-induced pulmonary fibrosis (day 3 through 56) in C57BL/6N mice. Western Blot analysis, assessment of Gpx activity, ELISA, and immunofluorescent stainings were used for validation and comparison with samples derived from interstitial lung disease patients.Results: GSH peroxidase 3 (Gpx3) was the only significantly increased GSH-metabolizing enzyme in BALF during bleomycin-induced lung fibrosis. This data was validated by Western Blot analysis and assessment of GPX activity in BALF.Immunofluorescent (IF) stainings revealed predominant expressionof Gpx3 by epithelial cells. Finally, BALF of ILD patients also contained high levels of GPX3. In tissue, however, Gpx7 was clearly upregulated and, as determined by IF co-stainings, localized to interstitial cells including myofibroblasts, while expression of Gpx1, the most abundant Gpx in tissue, appeared ubiquitous and remained largely unchanged.Conclusion: We show compartment-specific overexpression of selected Gpx during bleomycin-induced lung fibrosis. Hence, upregulation of Gpx enzymes might contribute to depletion of GSH in ELF and tissue, and thereby enhance the oxidant-antioxidant imbalance in pulmonary fibrosis. ER -