Quercetin improves epithelial regeneration from airway basal cells of COPD patients

• Published in: Respiratory research Vol. 25; no. 1; pp. 120 - 14
• Main Authors: McCluskey, Elizabeth S., Liu, Nathan, Pandey, Abhimaneu, Marchetti, Nathaniel, Kelsen, Steven G., Sajjan, Umadevi S.
• Format: Journal Article
• Language: English
• Published: London BioMed Central 11.03.2024; BioMed Central Ltd; Nature Publishing Group; BMC
• Subjects: Analysis; Anopheles; Antibodies; Basal cells; Bronchi - metabolism; Cell culture; Cell differentiation; Cell growth; Cells, Cultured; Chronic obstructive pulmonary disease; Clinical trials; Cytotoxicity; Development and progression; Dimethyl Sulfoxide - metabolism; Dimethyl Sulfoxide - pharmacology; DNA microarrays; ELF3; Enzyme-linked immunosorbent assay; Epigenetics; Epithelial Cells - metabolism; Epithelium; Flow cytometry; Gene expression; Genes; Genetic aspects; Goblet cell metaplasia; Goblet cells; Homeodomain Proteins - metabolism; Homeodomain Proteins - pharmacology; HOXB2; Humans; Hyperplasia; Interleukin 8; Interleukin-8 - metabolism; Kinases; Lung diseases; Lung diseases, Obstructive; Lungs; Medicine; Medicine & Public Health; Obstructive lung disease; Ontology; Patients; Placebos; Pneumology/Respiratory System; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - genetics; Quercetin; Quercetin - metabolism; Quercetin - pharmacology; Quercetin - therapeutic use; Regeneration; Respiratory tract diseases; RNA; Smoking; Stem cells; Transcription Factors - metabolism; Transforming growth factor-b; Transforming growth factors; Goblet cell metaplasia; HOXB2; Chronic obstructive pulmonary disease; ELF3
• ISSN: 1465-993X; 1465-9921; 1465-993X
• DOI: 10.1186/s12931-024-02742-0

Background Airway basal cells (BC) from patients with chronic obstructive pulmonary disease (COPD) regenerate abnormal airway epithelium and this was associated with reduced expression of several genes involved in epithelial repair. Quercetin reduces airway epithelial remodeling and inflammation in COPD models, therefore we examined whether quercetin promotes normal epithelial regeneration from COPD BC by altering gene expression. Methods COPD BC treated with DMSO or 1 µM quercetin for three days were cultured at air/liquid interface (ALI) for up to 4 weeks. BC from healthy donors cultured at ALI were used as controls. Polarization of cells was determined at 8 days of ALI. The cell types and IL-8 expression in differentiated cell cultures were quantified by flow cytometry and ELISA respectively. Microarray analysis was conducted on DMSO or 1 µM quercetin-treated COPD BC for 3 days to identify differentially regulated genes (DEG). Bronchial brushings obtained from COPD patients with similar age and disease status treated with either placebo (4 subjects) or 2000 mg/day quercetin (7 subjects) for 6 months were used to confirm the effects of quercetin on gene expression. Results Compared to placebo-, quercetin-treated COPD BC showed significantly increased transepithelial resistance, more ciliated cells, fewer goblet cells, and lower IL-8. Quercetin upregulated genes associated with tissue and epithelial development and differentiation in COPD BC. COPD patients treated with quercetin, but not placebo showed increased expression of two developmental genes HOXB2 and ELF3, which were also increased in quercetin-treated COPD BC with FDR < 0.001. Active smokers showed increased mRNA expression of TGF-β (0.067) and IL-8 (22.0), which was reduced by 3.6 and 4.14 fold respectively after quercetin treatment. Conclusions These results indicate that quercetin may improve airway epithelial regeneration by increasing the expression of genes involved in epithelial development/differentiation in COPD. Trial registration This study was registered at ClinicalTrials.gov on 6-18-2019. The study number is NCT03989271.