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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\u2019 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Primary airway smooth muscle cells (ASMC) were established from endobronchial biopsies obtained from patients with asthma (<jats:italic>n<\/jats:italic>\u2009=\u200910), patients with COPD (<jats:italic>n<\/jats:italic>\u2009=\u200910) and subjects that underwent diagnostic bronchoscopy without pathological findings and served as controls (<jats:italic>n<\/jats:italic>\u2009=\u20096). 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 GR\u03b1 and GR\u03b2 and HDACs was investigated in primary ASMC in the absence or in the presence of dexamethasone (10<jats:sup>\u2212\u20098<\/jats:sup>M) by western blotting. The complex formation of GR with transcription factors was assessed by co-immunoprecipitation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Expression of GR and its isoform GR\u03b1 but not GR\u03b2 was significantly reduced in ASMC from COPD patients as compared to controls. There were no significant differences in the expression of GR, GR\u03b1 and GR\u03b2 between responders and non-responders to ICS. However, treatment with dexamethasone upregulated the expression of total GR (<jats:italic>p<\/jats:italic>\u2009=\u20090.004) and GR\u03b1 (<jats:italic>p<\/jats:italic>\u2009=\u20090.005) after 30\u00a0min in responders but not in non-responders. \u03a4he formation of the complex GR-c-Jun was increased 60\u00a0min after treatment with dexamethasone only in responders who exhibited significantly lower expression of HDAC3 (<jats:italic>p<\/jats:italic>\u2009=\u20090.005) and HDAC5 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) as compared to non-responders.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These data suggest that ASMC from COPD patients who do not respond to treatment with ICS, are characterized by reduced GR-c-Jun complex formation and increased expression of HDAC3 and HDAC5.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>ISRCTN11017699 (Registration date: 15\/11\/2016).<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12931-024-02769-3","type":"journal-article","created":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T19:01:47Z","timestamp":1717009307000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Expression of glucocorticoid receptor and HDACs in airway smooth muscle cells is associated with response to steroids in COPD"],"prefix":"10.1186","volume":"25","author":[{"given":"Liang","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Papakonstantinou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Tamm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiana","family":"Stolz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,29]]},"reference":[{"key":"2769_CR1","doi-asserted-by":"publisher","first-page":"2222","DOI":"10.1056\/NEJMoa1516385","volume":"374","author":"JA Wedzicha","year":"2016","unstructured":"Wedzicha JA, Banerji D, Chapman KR, Vestbo J, Roche N, Ayers RT, et al. 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