{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:31:17Z","timestamp":1790299877169,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Patients with severe asthma (SA) are less responsive to the beneficial effects of corticosteroid (CS) therapy, and relative CS insensitivity has been shown in airway smooth muscle cells (ASMC) from patients with SA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We investigated whether there was a defect in the actions of the glucocorticoid receptor (GR) underlying the ability of CS to suppress the inflammatory response in ASMC of patients with SA. ASMC from healthy subjects (n = 10) and subjects with severe (n = 8) and nonsevere asthma (N-SA; n = 8) were cultured from endobronchial biopsies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>GR expression in ASMC from SA and N-SA was reduced compared with that from healthy subjects by 49% (P &amp;lt; 0.01). Although baseline levels of nuclear GR were similar, GR nuclear translocation induced by dexamethasone (10\u22127 M) in SA was 60% of that measured in either healthy subjects or subjects with N-SA. Tumor necrosis factor (TNF)-\u03b1 induced greater nuclear factor (NF)-\u03baB (p65) mRNA expression in ASMC from subjects with SA (5.6- vs. 2.0-fold; P &amp;lt; 0.01), whereas baseline and TNF-\u03b1\u2013induced nuclear translocation and dexamethasone-mediated suppression of p65 expression were similar between groups. Dexamethasone, although not modulating TNF-\u03b1\u2013induced p65 nuclear translocation, attenuated p65 recruitment to the CCL11 promoter in the healthy and N-SA groups, but this suppressive effect was impaired in subjects with SA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Decreased GR expression with impaired nuclear translocation in ASMC, associated with reduced dexamethasone-mediated attenuation of p65 recruitment to NF-\u03baB\u2013dependent gene promoters, may underlie CS insensitivity of severe asthma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201402-0314oc","type":"journal-article","created":{"date-parts":[[2014,11,20]],"date-time":"2014-11-20T15:43:26Z","timestamp":1416498206000},"page":"54-62","source":"Crossref","is-referenced-by-count":61,"title":["Impaired Nuclear Translocation of the Glucocorticoid Receptor in Corticosteroid-Insensitive Airway Smooth Muscle in Severe Asthma"],"prefix":"10.1093","volume":"191","author":[{"given":"Po-Jui","family":"Chang","sequence":"first","affiliation":[{"name":"Experimental Studies, Airway Disease Section, and"},{"name":"Biomedical Research Unit, Royal Brompton National Health Service Trust, London, United Kingdom; and"},{"name":"Department of Thoracic Medicine, Chang Gung Memorial Hospital and College of Medicine, Taoyuan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charalambos","family":"Michaeloudes","sequence":"additional","affiliation":[{"name":"Experimental Studies, Airway Disease Section, and"},{"name":"Biomedical Research Unit, Royal Brompton National Health Service Trust, London, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhu","sequence":"additional","affiliation":[{"name":"Lung Pathology Department, National Heart and Lung Institute, Imperial College London; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nooreen","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Experimental Studies, Airway Disease Section, and"},{"name":"Biomedical Research Unit, Royal Brompton National Health Service Trust, London, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Baker","sequence":"additional","affiliation":[{"name":"Experimental Studies, Airway Disease Section, and"},{"name":"Biomedical Research Unit, Royal Brompton National Health Service Trust, London, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kian Fan","family":"Chung","sequence":"additional","affiliation":[{"name":"Experimental Studies, Airway Disease Section, and"},{"name":"Biomedical Research Unit, Royal Brompton National Health Service Trust, London, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj K.","family":"Bhavsar","sequence":"additional","affiliation":[{"name":"Experimental Studies, Airway Disease Section, and"},{"name":"Biomedical Research Unit, Royal Brompton National Health Service Trust, London, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,1,1]]},"reference":[{"key":"2026032100233951700_bib1","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1164\/ajrccm.161.5.9903102","article-title":"Asthma. 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