# Sputum Glutaredoxin 1 and Protein S-Glutathionylation in COPD

## TL;DR

This study explores the role of glutaredoxin 1 and protein S-glutathionylation in COPD, linking them to lung function and inflammation during exacerbations.

## Contribution

The study identifies the Grx1/PSSG redox axis as a potential key player in COPD pathogenesis, particularly during acute exacerbations.

## Key findings

- PSSG levels decrease during COPD exacerbations, while Grx1 and total Grx activity increase.
- Grx1 levels correlate positively with lung function and negatively with inflammation markers.
- Grx1 modulates macrophage MMP expression and is secreted in response to inflammation.

## Abstract

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.