Airways glutathione S-transferase omega-1 and its A140D polymorphism are associated with severity of inflammation and respiratory dysfunction in cystic fibrosis

Background: Glutathione S-transferase omega-1 (GSTO1-1) is a cytosolic enzyme that modulates the Sthiolation status of intracellular factors involved in cancer cell survival or in the inflammatory response. Studies focusing on chronic obstructive pulmonary disease (COPD) have demonstrated that GSTO1-1 is detectable in alveolar macrophages, airway epithelium and in the extracellular compartment, where its functions have not been completely understood. Moreover GSTO1-1 polymorphisms have been associated with an increased risk to develop COPD. Against this background, the aim of this study was to evaluate GSTO1-1 levels and its polymorphisms in cystic fibrosis (CF) patients. Methods: Clinical samples from a previous study published by our groups were analyzed for GSTO1-1 levels and polymorphisms. For comparison, a model of lung inflammation in CFTR-knock out mice was also used. Results: Our data document that soluble GSTO1-1 can be found in the airways of CF patients and correlates with inflammatory parameters such as neutrophilic elastase and the chemokine IL-8. A negative correlation was found between GSTO1-1 levels and the spirometric parameter FEV1 and the FEV1/FVC ratio. Additionally, the A140D polymorphism of GSTO1-1 was associated with lower levels of the antiinflammatory mediators PGE2 and 15(S)-HETE, and with lower values of the FEV1/FVC ratio in CF subjects with the homozygous CFTR AF508 mutation. Conclusions: Our data suggest that extracellular GSTO1-1 and its polymorphysms could have a biological and clinical significance in CF. Pathophysiological functions of GSTOs are far from being completely understood, and more studies are required to understand the role(s) of extracellular GSTO1-1 in inflamed tissues. (C) 2021 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Automated summary

The study found soluble GSTO1-1 in the airways of CF patients, which was associated with inflammatory parameters and negatively correlated with lung function indicators FEV1 and FEV1/FVC ratio. Additionally, the A140D polymorphism of GSTO1-1 was linked to lower levels of anti-inflammatory mediators and decreased FEV1/FVC ratio in CF patients. Further research is needed to fully understand extracellular GSTO1-1's role in inflamed tissues.