PT  - JOURNAL ARTICLE
AU  - Andrea Schamberger
AU  - Herbert Schiller
AU  - Isis Fernandez
AU  - Martina Sterclova
AU  - Katharina Heinzelmann
AU  - Elisabeth Hennen
AU  - Rudolf Hatz
AU  - Jürgen Behr
AU  - Martina Vasakova
AU  - Matthias Mann
AU  - Oliver Eickelberg
AU  - Claudia Staab-Weijnitz
TI  - Glutathione peroxidase 3 localizes to the epithelial lining fluid and the extracellular matrix in lung fibrosis
AID  - 10.1183/13993003.congress-2016.PA781
DP  - 2016 Sep 01
TA  - European Respiratory Journal
PG  - PA781
VI  - 48
IP  - suppl 60
4099  - http://erj.ersjournals.com/content/48/suppl_60/PA781.short
4100  - http://erj.ersjournals.com/content/48/suppl_60/PA781.full
SO  - Eur Respir J2016 Sep 01; 48
AB  - Aberrant antioxidant activity contributes to the pathogenesis of interstitial lung diseases (ILD). The composition of the extracellular matrix (ECM) is affected by oxidative stress, but extracellular antioxidant defense mechanisms in ILD are incompletely understood.Here, relative abundance and detergent solubility of extracellular antioxidant enzymes were extracted from a proteomic dataset of bleomycin-induced lung fibrosis in C57BL/6N mice. Glutathione peroxidase (Gpx) activity was measured in bronchoalveolar lavage fluid (BALF) and immunofluorescent stainings were performed to address distribution of Gpx3 in the lung. Regulation of GPX3 by TGF-β1, TNF-α, and menadione was assessed in primary human bronchial epithelial cells (phBEC) and lung fibroblasts (phLF) by qPCR and ELISA. Finally, GPX3 levels were measured in BALF from ILD patients by ELISA.Sod3, Gpx3, and Gpx activity were increased in BALF of mice subjected to bleomycin-induced lung fibrosis. In total lung tissue, only Gpx3, but not Sod3, was upregulated. Quantitative detergent solubility profiles indicated that Gpx3, but not Sod3, associated with ECM proteins. Immunofluorescence analysis showed that Gpx3 was expressed by bronchial epithelial cells and interstitial fibroblasts and localized to the basement membrane and interstitial ECM in mouse and human lung tissue. GPX3 expression in phBEC and phLF was downregulated by TNF-α, but more variably regulated by TGF-β1 and menadione. BALF of some ILD patients contained high levels of GPX3.Hence, levels of the extracellular antioxidant enzyme GPX3 are variably increased in ILD. Upregulation of GPX3 might protect the ECM from oxidative damage in ILD.