Glucocorticoid receptor signaling in a bronchial epithelial cell line

The American Journal of Physiology
T D LeVanJ W Bloom

Abstract

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 (...Continue Reading

Citations

Feb 8, 2003·American Journal of Respiratory and Critical Care Medicine·Satoshi SuzukiZygmund S Krozowski
Aug 1, 2006·American Journal of Physiology. Lung Cellular and Molecular Physiology·André DagenaisYves Berthiaume

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