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Airways glutathione S-transferase omega-1 and its A140D polymorphism are associated with severity of inflammation and respiratory dysfunction in cystic fibrosis
- Source :
- Journal of Cystic Fibrosis. 20:1053-1061
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
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.
- 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
Subjects
Details
- ISSN :
- 15691993
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Journal of Cystic Fibrosis
- Accession number :
- edsair.doi.dedup.....7cce9f4ef88bacece51b5a499534863e