ArticleRespiratory research2016
Steroid resistance in COPD is associated with impaired molecular chaperone Hsp90 expression by pro-inflammatory lymphocytes.
Article in Respiratory research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- A Cross-Tissue Transcriptome Association Study Revealed Novel Susceptibility Genes for Chronic Obstructive Pulmonary Disease.International journal of chronic obstructive pulmonary disease · 2026Article
- Elevated Th1 and terminally differentiated cytotoxic T cells with suppressed Tc17 lymphocytes in lung tissue of advanced COPD and IPF patients undergoing lung transplantation.Frontiers in immunology · 2025Article
- Healthcare professionals' perception of the ketogenic diet among patients with chronic obstructive pulmonary disease: a cross-sectional study.Frontiers in nutrition · 2025Article
- The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the art.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Immunosenescence and Inflammation in Chronic Obstructive Pulmonary Disease: A Systematic Review.Journal of clinical medicine · 2024Review
- Applications and advancements of nanoparticle-based drug delivery in alleviating lung cancer and chronic obstructive pulmonary disease.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Glucocorticoids, their uses, sexual dimorphisms, and diseases: new concepts, mechanisms, and discoveries.Physiological reviews · 2024Review
- How inhaled corticosteroids target inflammation in COPD.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Polymer-Based Wound Dressings Loaded with Ginsenoside Rg3.Molecules (Basel, Switzerland) · 2023Review
- Organotypic sinonasal airway culture systems are predictive of the mucociliary phenotype produced by bronchial airway epithelial cells.Scientific reports · 2022Article
- COPD is associated with increased pro-inflammatory CD28null CD8 T and NKT-like cells in the small airways.Clinical and experimental immunology · 2022Article
- Accumulation of CD28Biomolecules · 2021Review
- Oxidative Stress Promotes Corticosteroid Insensitivity in Asthma and COPD.Antioxidants (Basel, Switzerland) · 2021Review
- Protective Role of Genetic Variants in HSP90 Genes-Complex in COPD Secondary to Biomass-Burning Smoke Exposure and Non-Severe COPD Forms in Tobacco Smoking Subjects.Current issues in molecular biology · 2021Article
- Bronchial thermoplasty in asthma: an exploratory histopathological evaluation in distinct asthma endotypes/phenotypes.Respiratory research · 2021Observational
- Insights into the antitumor mechanism of ginsenosides Rg3.Molecular biology reports · 2021Review
- Fractional heat shock protein 27 urine excretion as a short-term predictor in acute exacerbation of chronic obstructive pulmonary disease.Annals of translational medicine · 2021Article
- Heat shock protein 27 as a predictor of prognosis in patients admitted to hospital with acute COPD exacerbation.Cell stress & chaperones · 2020Article
- COPD-Related Modification to the Airway Epithelium Permits Intracellular Residence of NontypeableInternational journal of chronic obstructive pulmonary disease · 2020Article
- Determining Pharmacological Mechanisms of Chinese Incompatible Herbs Fuzi and Banxia in Chronic Obstructive Pulmonary Disease: A Systems Pharmacology-Based Study.Evidence-based complementary and alternative medicine : eCAM · 2020Article
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Authors and funding
7 authors.
Funding
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Abstract
backgroundCorticosteroid resistance is a major barrier to effective treatment of COPD. We have shown that the resistance is associated with decreased expression of glucocorticoid receptor (GCR) by senescent CD28nullCD8+ pro-inflammatory lymphocytes in peripheral blood of COPD patients. GCR must be bound to molecular chaperones heat shock proteins (Hsp) 70 and Hsp90 to acquire a high-affinity steroid binding conformation, and traffic to the nucleus. We hypothesized a loss of Hsp70/90 from these lymphocytes may further contribute to steroid resistance in COPD.
methodsBlood was collected from COPD (n = 10) and aged-matched controls (n = 10). To assess response to steroids, cytotoxic mediators, intracellular pro-inflammatory cytokines, CD28, GCR, Hsp70 and Hsp90 were determined in T and NKT-like cells in the presence of ± 10 μM prednisolone and 2.5 ng/mL cyclosporine A (binds to GCR-Hsp70/90 complex) using flow cytometry, western blot and fluorescence microscopy.
resultsA loss of expression of Hsp90 and GCR from CD28null CD8+ T and NKT-like cells in COPD was noted (Hsp70 unchanged). Loss of Hsp90 expression correlated with the percentage of CD28null CD8+ T and NKT-like cells producing IFNγ or TNFα in all subjects (eg, COPD: R = -0.763, p = 0.007 for T-cell IFNγ). Up-regulation of Hsp90 and associated decrease in pro-inflammatory cytokine production was found in CD28nullCD8+ T and NKT-like cells in the presence of 10 μM prednisolone and 2.5 ng/mL cyclosporine A.
conclusionsLoss of Hsp90 from cytotoxic/pro-inflammatory CD28nullCD8+ T and NKT-like cells could contribute to steroid resistance in COPD. Combination prednisolone and low-dose cyclosporine A therapy inhibits these pro-inflammatory cells and may reduce systemic inflammation in COPD.
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