{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:19:42Z","timestamp":1774617582430,"version":"3.50.1"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2000,1,1]],"date-time":"2000-01-01T00:00:00Z","timestamp":946684800000},"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":[[2000,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We determined whether inhaled corticosteroid therapy modulates the expression of the transcription factor, nuclear factor kappa B (NF- \u03ba B), in patients with asthma. Fifteen stable patients with mild asthma underwent bronchoalveolar lavage (BAL) with bronchial biopsies in a double-blind, placebo-controlled and crossover study after placebo or after inhaled fluticasone propionate (500 \u03bc g twice daily). Fluticasone reduced the number of eosinophils in BAL fluid (BALF) and in airway biopsies, together with an improvement of bronchial responsiveness to methacholine. However, NF- \u03ba B DNA-binding in alveolar macrophages and in bronchial biopsies was not affected by fluticasone treatment. NF- \u03ba B expression was also measured by immunohistochemical staining with an antibody to the p65 component of NF- \u03ba B. Fluticasone caused an increase in the number of positive nuclear staining cells in the airway epithelium from 34.1 \u00b1 5.0 to 64.1 \u00b1 8.0 per mm2 (p = 0.002). In vitro studies of A549 epithelial cells stimulated by interleukin-1 \u03b2 (IL-1 \u03b2 ) showed that dexamethasone increased p65 protein expression analyzed by Western blot. Despite an anti-inflammatory effect of fluticasone, there was no decrease in NF- \u03ba B\u2013DNA binding and activation, indicating that this may not be a mechanism by which corticosteroids act in asthma. The significance of corticosteroid-induced increase in p65 protein expression is not known. Hart L, Lim S, Adcock I, Barnes PJ, Chung KF. Effects of inhaled corticosteroid therapy on expression and DNA-binding activity of nuclear factor \u03ba B in asthma.<\/jats:p>","DOI":"10.1164\/ajrccm.161.1.9809019","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T14:08:10Z","timestamp":1365084490000},"page":"224-231","source":"Crossref","is-referenced-by-count":78,"title":["Effects of Inhaled Corticosteroid Therapy on Expression and DNA-Binding Activity of Nuclear Factor \u03ba B in Asthma"],"prefix":"10.1093","volume":"161","author":[{"given":"LORRAINE","family":"HART","sequence":"first","affiliation":[{"name":"Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine and Royal Brompton Hospital, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"SAM","family":"LIM","sequence":"additional","affiliation":[{"name":"Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine and Royal Brompton Hospital, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"IAN","family":"ADCOCK","sequence":"additional","affiliation":[{"name":"Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine and Royal Brompton Hospital, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"PETER J.","family":"BARNES","sequence":"additional","affiliation":[{"name":"Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine and Royal Brompton Hospital, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"FAN CHUNG","sequence":"additional","affiliation":[{"name":"Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine and Royal Brompton Hospital, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2000,1,1]]},"reference":[{"key":"2026032708342992000_B1","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1056\/NEJM199503303321307","article-title":"Inhaled glucocorticoids for asthma.","volume":"332","author":"Barnes","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"2026032708342992000_B2","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1164\/ajrccm.149.1.8111605","article-title":"Inhaled beclomethasone dipropionate downregulates airway lymphocyte activation in atopic asthma.","volume":"149","author":"Wilson","year":"1994","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026032708342992000_B3","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/S0091-6749(06)80008-4","article-title":"A comparative study of the effects of an inhaled corticosteroid, budesonide, and of a \u03b22-agonist, terbutaline, on airway inflammation in newly diagnosed asthma: a randomized, double-blind, parallel-group controlled trial.","volume":"90","author":"Laitinen","year":"1992","journal-title":"J. Allergy Clin. Immunol."},{"key":"2026032708342992000_B4","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1164\/ajrccm\/148.2.401","article-title":"Prednisolone treatment in asthma is associated with modulation of bronchoalveolar lavage cell IL-4, IL-5 and IFN-\u03b3 cytokine gene expression.","volume":"148","author":"Robinson","year":"1993","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032708342992000_B5","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1164\/ajrccm.153.2.8564096","article-title":"Prednisolone treatment in asthma: reduction in the numbers of eosinophils, T cells, tryptase-only positive mast cells, and modulation of IL-4, IL-5, and interferon-gamma cytokine gene expression within the bronchial mucosa.","volume":"153","author":"Bentley","year":"1996","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026032708342992000_B6","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1164\/ajrccm\/147.6_Pt_1.1557","article-title":"Detection of GM-CSF in asthmatic bronchial epithelium and decrease by inhaled corticosteroids.","volume":"147","author":"Sousa","year":"1993","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032708342992000_B7","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1165\/ajrcmb.14.1.8534483","article-title":"Expression of RANTES by human bronchial epithelial cells in vitro and in vivo and the effect of corticosteroids.","volume":"14","author":"Wang","year":"1996","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026032708342992000_B8","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1172\/JCI115166","article-title":"Expression of mRNA for interleukins in mucosal bronchial biopsies from asthma.","volume":"87","author":"Hamid","year":"1991","journal-title":"J. Clin. Invest."},{"key":"2026032708342992000_B9","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1172\/JCI113301","article-title":"Dexamethasone inhibition of interleukin 1 beta production by human monocytes: posttranscriptional mechanisms.","volume":"81","author":"Kern","year":"1988","journal-title":"J. Clin. Invest."},{"key":"2026032708342992000_B10","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1046\/j.1365-2567.1996.477579.x","article-title":"Expression of RANTES in human airway epithelial cells: effect of corticosteroids and interleukin-4, 10 and 13.","volume":"87","author":"Berkman","year":"1995","journal-title":"Immunology"},{"key":"2026032708342992000_B11","first-page":"389","article-title":"Inhibition of interleukin-8 expression by dexamethasone in human cultured airway epithelial cells.","volume":"81","author":"Kwon","year":"1994","journal-title":"Immunology"},{"key":"2026032708342992000_B12","first-page":"494","article-title":"Inhibition of interleukin-5 gene expression by dexamethasone.","volume":"77","author":"Rolfe","year":"1992","journal-title":"Immunology"},{"key":"2026032708342992000_B13","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/0092-8674(89)90237-7","article-title":"Gene regulation by steroid hormones.","volume":"56","author":"Beato","year":"1989","journal-title":"Cell"},{"key":"2026032708342992000_B14","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1073\/pnas.91.2.752","article-title":"Physical association and functional antagonism between p65 subunit of transcription factor NF-\u03baB and the glucocorticoid receptor.","volume":"91","author":"Ray","year":"1994","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026032708342992000_B15","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1128\/MCB.15.2.943","article-title":"Characterization of mechanisms involved in transrepression of NF-\u03baB by activated glucocorticoid receptors.","volume":"15","author":"Scheinman","year":"1995","journal-title":"Mol. Cell. Biol."},{"key":"2026032708342992000_B16","doi-asserted-by":"crossref","first-page":"C331","DOI":"10.1152\/ajpcell.1995.268.2.C331","article-title":"The effects of glucocorticoids on transcription activation in human peripheral blood mononuclear cells.","volume":"37","author":"Adcock","year":"1995","journal-title":"Am. J. Physiol."},{"key":"2026032708342992000_B17","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/0165-6147(93)90184-L","article-title":"Anti-inflammatory actions of steroids: molecular mechanisms.","volume":"14","author":"Barnes","year":"1993","journal-title":"Trends Pharmacol. Sci."},{"key":"2026032708342992000_B18","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1056\/NEJM199704103361506","article-title":"Nuclear factor-\u03baB: a pivotal transcription factor in chronic inflammatory diseases.","volume":"336","author":"Barnes","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"2026032708342992000_B19","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1146\/annurev.iy.12.040194.001041","article-title":"Function and activation of NF-\u03baB in the immune system.","volume":"12","author":"Baeuerle","year":"1994","journal-title":"Annu. Rev. Immunol."},{"key":"2026032708342992000_B20","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1146\/annurev.immunol.14.1.649","article-title":"The NF-\u03baB and I\u03baB proteins: new discoveries and insights.","volume":"14","author":"Baldwin","year":"1996","journal-title":"Annu. Rev. Immunol."},{"key":"2026032708342992000_B21","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1164\/ajrccm.158.5.9706116","article-title":"Activation and localisation of transcription factor, nuclear factor-\u03baB, in asthma.","volume":"158","author":"Hart","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026032708342992000_B22","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1146\/annurev.cb.10.110194.002201","article-title":"Structure, regulation and function of NF-\u03baB.","volume":"10","author":"Siebenlist","year":"1994","journal-title":"Annu. Rev. Cell Biol."},{"key":"2026032708342992000_B23","first-page":"6231","article-title":"Characterization of a functional NF-\u03baB site in the human interleukin 1 beta promoter: evidence for a positive autoregulatory loop.","volume":"13","author":"Hiscott","year":"1993","journal-title":"Mol. Cell. Biol."},{"key":"2026032708342992000_B24","doi-asserted-by":"crossref","first-page":"4705","DOI":"10.1016\/S0021-9258(17)37600-7","article-title":"Role of transcription factor NF-\u03baB\/Rel in induction of nitric oxide synthase.","volume":"269","author":"Xie","year":"1994","journal-title":"J. Biol. Chem."},{"key":"2026032708342992000_B25","doi-asserted-by":"crossref","first-page":"4996","DOI":"10.4049\/jimmunol.150.11.4996","article-title":"Genomic cloning and promoter analysis of macrophage inflammatory protein (MIP)-2, MIP-1\u03b1, and MIP-1\u03b2, members of the chemokine superfamily of proinflammatory cytokines.","volume":"150","author":"Widmer","year":"1993","journal-title":"J. Immunol."},{"key":"2026032708342992000_B26","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.4049\/jimmunol.157.3.1139","article-title":"Identification of a novel regulatory region critical for expression of the RANTES chemokine in activated T lymphocytes.","volume":"157","author":"Nelson","year":"1996","journal-title":"J. Immunol."},{"key":"2026032708342992000_B27","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1126\/science.270.5234.286","article-title":"Immunosuppression by glucocorticoids: inhibition of NF-\u03baB activity through induction of I\u03ba-B synthesis.","volume":"270","author":"Auphan","year":"1995","journal-title":"Science"},{"key":"2026032708342992000_B28","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/0024-3205(94)00243-6","article-title":"The effects of glucocorticoids on phorbol ester and cytokine stimulated transcription factor activation in human lung.","volume":"55","author":"Adcock","year":"1994","journal-title":"Life Sci."},{"key":"2026032708342992000_B29","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1046\/j.1432-1327.1998.2540081.x","article-title":"Effect of dexamethasone on interleukin-1beta-(IL-1beta)-induced nuclear factor-kappaB (NF-\u03baB) and \u03baB-dependent transcription in epithelial cells.","volume":"254","author":"Newton","year":"1998","journal-title":"Eur. J. Biochem."},{"key":"2026032708342992000_B30","doi-asserted-by":"crossref","first-page":"534","DOI":"10.4049\/jimmunol.159.2.534","article-title":"Dexamethasone potently enhances phorbol ester-induced IL-1beta gene expression and nuclear factor NF-\u03baB activation.","volume":"159","author":"Wang","year":"1997","journal-title":"J. Immunol."},{"key":"2026032708342992000_B31","doi-asserted-by":"crossref","first-page":"19612","DOI":"10.1074\/jbc.271.32.19612","article-title":"Glucocorticoid-mediated repression of NF-\u03baB activity in endothelial cells does not involve induction of IkappaBalpha synthesis.","volume":"271","author":"Brostjan","year":"1996","journal-title":"J. Biol. Chem."},{"key":"2026032708342992000_B32","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0003-2697(88)90164-9","article-title":"Rapid and quantitative preparation of cytoplasmic RNA from small numbers of cells.","volume":"173","author":"Gough","year":"1988","journal-title":"Anal. Biochem."},{"key":"2026032708342992000_B33","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1073\/pnas.86.7.2336","article-title":"TNF-\u03b1 and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the NF-\u03baB.","volume":"86","author":"Osborn","year":"1989","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026032708342992000_B34","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1093\/nar\/11.5.1475","article-title":"Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei.","volume":"11","author":"Dignan","year":"1983","journal-title":"Nucleic Acids Res."},{"key":"2026032708342992000_B35","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/0304-3940(88)90346-1","article-title":"The glucose oxidase\u2013DAB\u2013nickel method in peroxidase histochemistry of the central nervous system.","volume":"85","author":"Shu","year":"1988","journal-title":"Neurosci. Lett."},{"key":"2026032708342992000_B36","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3109\/10715769209079515","article-title":"Nuclear factor \u03baB: an oxidative stress-responsive transcription factor of eukaryotic cells (a review).","volume":"17","author":"Schreck","year":"1992","journal-title":"Free Rad. Res. Commun."},{"key":"2026032708342992000_B37","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1006\/bbrc.1994.1403","article-title":"Oxidative stress induces NF-\u03baB DNA binding and inducible NOS mRNA in human epithelial cells.","volume":"199","author":"Adcock","year":"1994","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2026032708342992000_B38","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1164\/ajrccm.154.4.8887608","article-title":"Expression of interleukin-1 beta (IL-1beta) and interleukin-1 receptor antagonist (IL-1ra) on asthmatic bronchial epithelium.","volume":"154","author":"Sousa","year":"1996","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026032708342992000_B39","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1111\/j.1365-2222.1991.tb03205.x","article-title":"TNF-\u03b1 mRNA expression in allergic inflammation.","volume":"21","author":"Ying","year":"1991","journal-title":"Clin. Exp. Allergy"},{"key":"2026032708342992000_B40","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1172\/JCI118431","article-title":"Rhinovirus stimulation of interleukin-6 in vivo and in vitro: evidence for nuclear factor-\u03baB-dependent transcriptional activation.","volume":"97","author":"Zhu","year":"1996","journal-title":"J. Clin. Invest"},{"key":"2026032708342992000_B41","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/0014-5793(95)00333-5","article-title":"Dexamethasone inhibits ozone-induced gene expression of macrophage inflammatory protein-2 in rat lung.","volume":"363","author":"Haddad","year":"1995","journal-title":"FEBS Lett."},{"key":"2026032708342992000_B42","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1165\/ajrcmb\/7.2.128","article-title":"C-fos proto-oncogene expression in bronchial biopsies of asthmatics.","volume":"7","author":"Demoly","year":"1992","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026032708342992000_B43","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1183\/09031936.94.07122117","article-title":"Effects of dexamethasone on cytokine and phorbol ester stimulated c-Fos and c-Jun DNA binding and gene expression in human lung.","volume":"7","author":"Adcock","year":"1994","journal-title":"Eur. Respir. J."},{"key":"2026032708342992000_B44","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1136\/thx.53.7.577","article-title":"Glucocorticoids decrease c-fos expression in human nasal polyps in vivo.","volume":"53","author":"Baraniuk","year":"1998","journal-title":"Thorax"},{"key":"2026032708342992000_B45","doi-asserted-by":"crossref","first-page":"19680","DOI":"10.1074\/jbc.271.33.19680","article-title":"Identification of signal-induced I\u03baB-alpha kinases in human endothelial cells.","volume":"271","author":"Bennett","year":"1996","journal-title":"J. Biol. Chem."}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/161\/1\/224\/67423533\/ajrccm_161_1_224.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/161\/1\/224\/67423533\/ajrccm_161_1_224.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:34:37Z","timestamp":1774614877000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/161\/1\/224\/8527309"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,1,1]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2000,1,1]]},"published-print":{"date-parts":[[2000,1,1]]}},"URL":"https:\/\/doi.org\/10.1164\/ajrccm.161.1.9809019","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2000,1]]},"published":{"date-parts":[[2000,1,1]]}}}