Document Detail

Glucocorticoid receptor signaling in a bronchial epithelial cell line.
MedLine Citation:
PMID:  9176246     Owner:  NLM     Status:  MEDLINE    
Glucocorticoids are an effective anti-inflammatory therapy for the treatment of asthma. The anti-inflammatory effects of glucocorticoids may be due to the inhibition of transcription factors that regulate cytokine synthesis. Because of the potential role of the bronchial epithelium in asthmatic inflammation and the possibility that this cell may be the main target of inhaled glucocorticoids, we have characterized glucocorticoid receptors (GR) and GR signaling in the human bronchial epithelial cell line BEAS-2B. Western blot analysis and radioligand binding studies demonstrated that BEAS-2B cells have functional GR that bind to dexamethasone (Dex) (dissociation constant = 5.6 nM and maximal density of binding sites = 228 +/- 3.3 fmol/mg protein). GR were activated by Dex as assessed using a glucocorticoid-responsive reporter plasmid. Transfection of BEAS-2B cells with an activator protein-1 (AP-1) reporter construct followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment resulted in a fivefold induction of reporter gene activity. Transfection with a nuclear factor (NF)-kappa B reporter construct followed by tumor necrosis factor-alpha (TNF-alpha) treatment resulted in a 10-fold induction of reporter gene activity. Dex (10(-7) M) markedly repressed both the induced AP-1 and NF-kappa B activity. The GR antagonist RU-486 inhibited the repressive effect of Dex on TNF-alpha-induced NF-kappa B activity by 81% but only counteracted the repressive effect of Dex on TPA-induced AP-1 activity by 43%. These studies demonstrate that cross-signaling between AP-1 and NF-kappa B with GR may explain the anti-inflammatory properties of glucocorticoids in airway epithelial cells.
T D LeVan; F D Behr; K K Adkins; R L Miesfeld; J W Bloom
Related Documents :
15145446 - Differential expression of 11beta-hydroxysteroid dehydrogenase types 1 and 2 mrna and g...
17699566 - Long-term hypoxia modulates expression of key genes regulating adrenomedullary function...
21503876 - Microrna-181b and microrna-9 mediate arsenic-induced angiogenesis via nrp1.
11014236 - Circadian and glucocorticoid regulation of rev-erbalpha expression in liver.
17477366 - Expression of the forkhead transcription factor foxp1 is associated both with hypoxia i...
21871426 - P52 activation in monomorphic b-cell posttransplant lymphoproliferative disorder/diffus...
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  272     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1997 May 
Date Detail:
Created Date:  1997-07-08     Completed Date:  1997-07-08     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  L838-43     Citation Subset:  IM    
Respiratory Sciences Center, University of Arizona, Tucson 85724, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Bronchi / cytology,  drug effects,  metabolism*
Cell Line
Dexamethasone / pharmacology
Epithelial Cells
Epithelium / drug effects,  metabolism
Glucocorticoids / pharmacology
NF-kappa B / antagonists & inhibitors
Receptors, Glucocorticoid / genetics,  physiology*
Signal Transduction*
Transcription Factor AP-1 / antagonists & inhibitors
Transcription, Genetic
Transcriptional Activation
Grant Support
Reg. No./Substance:
0/Glucocorticoids; 0/NF-kappa B; 0/Receptors, Glucocorticoid; 0/Transcription Factor AP-1; 50-02-2/Dexamethasone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Type II pneumocytes release chemoattractant activity for monocytes constitutively.
Next Document:  Sex hormones regulate CFTR in developing fetal rat lung epithelial cells.