Expression of glucocorticoid receptor and HDACs in airway smooth muscle cells is associated with response to steroids in COPD

作者：Liang Zhou, Michael Roth, Eleni Papakonstantinou, Michael Tamm, Daiana Stolz · 发表于：Respiratory Research · 年份：2024 · DOI：10.1186/s12931-024-02769-3 · 被引用次数：11 · 研究领域：Asthma and respiratory diseases、Chronic Obstructive Pulmonary Disease (COPD) Research、Adrenal Hormones and Disorders

Abstract Background Steroid insensitivity in Chronic Obstructive Pulmonary Disease (COPD) presents a problem for controlling the chronic inflammation of the airways. The glucocorticoid receptor (GR) mediates the intracellular signaling of inhaled corticosteroids (ICS) by interacting with transcription factors and histone deacetylases (HDACs). The aim of this study was to assess if COPD patients’ response to ICS in vivo, may be associated with the expression of GR, the complex of GR with transcription factors, and the expression of various HDACs in vitro. Methods Primary airway smooth muscle cells (ASMC) were established from endobronchial biopsies obtained from patients with asthma (n = 10), patients with COPD (n = 10) and subjects that underwent diagnostic bronchoscopy without pathological findings and served as controls (n = 6). ASMC were also established from 18 COPD patients, 10 responders and 8 non-responders to ICS, who participated in the HISTORIC study, an investigator-initiated and driven clinical trial that proved the hypothesis that COPD patients with high ASMC in their endobronchial biopsies respond better to ICS than patients with low ASMC. Expression of GR and its isoforms GRα and GRβ and HDACs was investigated in primary ASMC in the absence or in the presence of dexamethasone (10− 8M) by western blotting. The complex formation of GR with transcription factors was assessed by co-immunoprecipitation. Results Expression of GR and its isoform GRα but not GRβ was si...