ArticleThe Journal of allergy and clinical immunology2015
Cysteine oxidation impairs systemic glucocorticoid responsiveness in children with difficult-to-treat asthma.
Article in The Journal of allergy and clinical immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
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Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 26 citations in OpenAlex.
- Effects of perioperative oxygen concentration on oxidative stress in adult surgical patients: a systematic review.British journal of anaesthesia · 2021Pooled it
- A Review of CXCL1 in Cardiac Fibrosis.Frontiers in cardiovascular medicine · 2021Pooled it
- Rare constituents of the nasal microbiome contribute to the acute exacerbation of chronic rhinosinusitis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- L-serine metabolic regulation and host respiratory homeostasis.Frontiers in cellular and infection microbiology · 2025Review
- Metabolomics identifies disturbances in arginine, phenylalanine, and glycine metabolism as differentiating features of exacerbating atopic asthma in children.The journal of allergy and clinical immunology. Global · 2023Article
- Use of thiols and implications for the use of inhaled corticosteroids in the presence of oxidative stress in COPD.Respiratory research · 2023Review
- Oxidative Stress, Environmental Pollution, and Lifestyle as Determinants of Asthma in Children.Biology · 2023Review
- Exercise Training Induces a Shift in Extracellular Redox Status with Alterations in the Pulmonary and Systemic Redox Landscape in Asthma.Antioxidants (Basel, Switzerland) · 2021Article
- Oxidative Stress Promotes Corticosteroid Insensitivity in Asthma and COPD.Antioxidants (Basel, Switzerland) · 2021Review
- Defining a role for exercise training in the management of asthma.European respiratory review : an official journal of the European Respiratory Society · 2020Review
- The mercapturomic profile of health and non-communicable diseases.High-throughput · 2019Review
- Asthma and Corticosteroid Responses in Childhood and Adult Asthma.Clinics in chest medicine · 2019Review
- The Reactive Species Interactome: Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine.Antioxidants & redox signaling · 2017Review
- Severe Asthma in Children: Lessons Learned and Future Directions.The journal of allergy and clinical immunology. In practiceReview
- Systemic Corticosteroid Responses in Children with Severe Asthma: Phenotypic and Endotypic Features.The journal of allergy and clinical immunology. In practiceArticle
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe mechanisms underlying glucocorticoid responsiveness are largely unknown. Although redox regulation of the glucocorticoid receptor (GR) has been reported, it has not been studied in asthmatic patients.
objectiveWe characterized systemic cysteine oxidation and its association with inflammatory and clinical features in healthy children and children with difficult-to-treat asthma. We hypothesized that cysteine oxidation would be associated with increased markers of oxidative stress and inflammation, increased features of asthma severity, decreased clinically defined glucocorticoid responsiveness, and impaired GR function.
methodsPBMCs were collected from healthy children (n = 16) and children with asthma (n = 118) aged 6 to 17 years. Children with difficult-to-treat asthma underwent glucocorticoid responsiveness testing with intramuscular triamcinolone. Cysteine, cystine, and inflammatory chemokines and reactive oxygen species generation were quantified, and expression and activity of the GR were assessed.
resultsCysteine oxidation was present in children with difficult-to-treat asthma and accompanied by increased reactive oxygen species generation and increased CCL3 and CXCL1 mRNA expression. Children with the greatest extent of cysteine oxidation had more features of asthma severity, including poorer symptom control, greater medication use, and less glucocorticoid responsiveness despite inhaled glucocorticoid therapy. Cysteine oxidation also modified the GR protein by decreasing available sulfhydryl groups and decreasing nuclear GR expression and activity.
conclusionsA highly oxidized cysteine redox state promotes a posttranslational modification of the GR that might inhibit its function. Given that cysteine oxidation is prevalent in children with difficult-to-treat asthma, the cysteine redox state might represent a potential therapeutic target for restoration of glucocorticoid responsiveness in this population.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.