1. Airways glutathione S-transferase omega-1 and its A140D polymorphism are associated with severity of inflammation and respiratory dysfunction in cystic fibrosis
- Author
-
Claudio Sorio, Elisabetta Marchi, Alfonso Pompella, Riccardo Zucchi, Matthias Griese, Alessandro Corti, Vittoria Carnicelli, Andreas Hector, Simona Piaggi, University of Zurich, and Corti, Alessandro
- Subjects
Pulmonary and Respiratory Medicine ,610 Medicine & health ,Inflammation ,Polymorphism, Single Nucleotide ,Severity of Illness Index ,Cystic fibrosis ,cystic fibrosis ,Mice ,FEV1 ,FEV1/FVC ratio ,medicine ,Extracellular ,Animals ,Humans ,2735 Pediatrics, Perinatology and Child Health ,A140D polymorphism ,gamma-glutamyltransferase ,Glutathione S-transferase omega-1-1 ,GSTO1-1 ,lung inflammation ,Gamma-glutamyltransferase ,Glutathione Transferase ,COPD ,Lung ,biology ,business.industry ,respiratory system ,medicine.disease ,Respiratory Function Tests ,respiratory tract diseases ,Mice, Inbred C57BL ,Disease Models, Animal ,Glutathione S-transferase omega-1-1 GSTO1-1 A140D polymorphism lung inflammation cystic fibrosis FEV1 FEV1/FVC ratio gamma-glutamyltransferase ,medicine.anatomical_structure ,10036 Medical Clinic ,2740 Pulmonary and Respiratory Medicine ,Pediatrics, Perinatology and Child Health ,Immunology ,biology.protein ,Respiratory epithelium ,medicine.symptom ,Carrier Proteins ,business - Abstract
Background Glutathione S-transferase omega-1 (GSTO1-1) is a cytosolic enzyme that modulates the S-thiolation 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 ΔF508 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.
- Published
- 2021