ERJ
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Permissions
Right arrowRequest Permissions
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Verheggen, M.
Right arrow Articles by Versnel, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Verheggen, M.
Right arrow Articles by Versnel, M.
Eur Respir J 1996; 9: 2036-2043
Copyright © ERS Journals Ltd 1996

Original Articles

Modulation of glucocorticoid receptor expression in human bronchial epithelial cell lines by IL-1 beta, TNF-alpha and LPS

MM Verheggen, PT van Hal, PW Adriaansen-Soeting, BJ Goense, HC Hoogsteden, AO Brinkmann, and MA Versnel

Bronchial epithelium plays a major role in the regulation of inflammatory reactions in the airways. It is thought to be a possible target for glucocorticoid therapy. Glucocorticoid responsiveness requires the presence of specific glucocorticoid receptors (GR). Until now, little was known about the presence of such receptors in the human bronchial epithelium. In this study we demonstrated the expression of GR messenger ribonucleic acid (mRNA) in two simian virus (SV)-40/adenovirus-transformed human bronchial epithelial cell lines, BEAS S6 and BEAS 2B. In a whole cell dexamethasone binding assay, BEAS S6 and BEAS 2B cells were found to possess (mean +/- SEM) 28.9 +/- 4.4 x 10(3) and 32.1 +/- 5.7 x 10(3) binding sites per cell, respectively, with dissociation constant (Kd) values of 8.2 +/- 1.5 and 8.6 +/- 2.4 nM, respectively. Using electrophoretic mobility shift assays we demonstrated the binding of nuclear translocated GR to specific sites on deoxyribonucleic acid (DNA), named glucocorticoid responsive elements (GRE). Lipopolysaccharide (LPS) and interleukin-1 beta (IL-1 beta) significantly increased the number of GR per cell (median = 312% and 171% of control, respectively; p < 0.05), but significantly reduced the ligand affinity of these receptors, i.e. increased the Kd (median = 410% and 145% of control, respectively; p < 0.05) in BEAS 2B cells. These results indicate that the bronchial epithelium may be an actual target for glucocorticoid therapy. Inflammatory mediators, such as IL-1 beta and LPS, modulate the number and ligand affinity of these GR. Therefore, the response of bronchial epithelium to glucocorticoid therapy may be modulated by airway diseases associated with inflammation.


This article has been cited by other articles:


Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. Hu, S. Fatma, J. Cao, J. S. Grunstein, G. Nino, Y. Grumbach, and M. M. Grunstein
Th2 cytokine-induced upregulation of 11{beta}-hydroxysteroid dehydrogenase-1 facilitates glucocorticoid suppression of proasthmatic airway smooth muscle function
Am J Physiol Lung Cell Mol Physiol, May 1, 2009; 296(5): L790 - L803.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
A. Kariagina, S. Zonis, M. Afkhami, D. Romanenko, and V. Chesnokova
Leukemia inhibitory factor regulates glucocorticoid receptor expression in the hypothalamic-pituitary-adrenal axis
Am J Physiol Endocrinol Metab, November 1, 2005; 289(5): E857 - E863.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Y. Zhang, X. Ding, and R. A. Daynes
The Expression of 11{beta}-Hydroxysteroid Dehydrogenase Type I by Lymphocytes Provides a Novel Means for Intracrine Regulation of Glucocorticoid Activities
J. Immunol., January 15, 2005; 174(2): 879 - 889.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
L Pujols, A Xaubet, J Ramirez, J Mullol, J Roca-Ferrer, A Torrego, J A Cidlowski, and C Picado
Expression of glucocorticoid receptors {alpha} and {beta} in steroid sensitive and steroid insensitive interstitial lung diseases
Thorax, August 1, 2004; 59(8): 687 - 693.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
B. BARTHOLOME, C. M. SPIES, T. GABER, S. SCHUCHMANN, T. BERKI, D. KUNKEL, M. BIENERT, A. RADBRUCH, G.-R. BURMESTER, R. LAUSTER, et al.
Membrane glucocorticoid receptors (mGCR) are expressed in normal human peripheral blood mononuclear cells and up-regulated after in vitro stimulation and in patients with rheumatoid arthritis
FASEB J, January 1, 2004; 18(1): 70 - 80.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
C. de Coupade, M. N. Ajuebor, F. Russo-Marie, M. Perretti, and E. Solito
Cytokine Modulation of Liver Annexin 1 Expression during Experimental Endotoxemia
Am. J. Pathol., October 1, 2001; 159(4): 1435 - 1443.
[Abstract] [Full Text]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
L. Pujols, J. Mullol, M. Pérez, J. Roca-Ferrer, M. Juan, A. Xaubet, J. A. Cidlowski, and C. Picado
Expression of the Human Glucocorticoid Receptor {alpha} and {beta} Isoforms in Human Respiratory Epithelial Cells and Their Regulation by Dexamethasone
Am. J. Respir. Cell Mol. Biol., January 1, 2001; 24(1): 49 - 57.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
A. Bellocq, S. Doublier, S. Suberville, J. Perez, B. Escoubet, B. Fouqueray, D. R. Puyol, and L. Baud
Somatostatin Increases Glucocorticoid Binding and Signaling in Macrophages by Blocking the Calpain-specific Cleavage of Hsp 90
J. Biol. Chem., December 24, 1999; 274(52): 36891 - 36896.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. M. Pariante, B. D. Pearce, T. L. Pisell, C. I. Sanchez, C. Po, C. Su, and A. H. Miller
The Proinflammatory Cytokine, Interleukin-1{alpha}, Reduces Glucocorticoid Receptor Translocation and Function
Endocrinology, September 1, 1999; 140(9): 4359 - 4366.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1996 by the European Respiratory Society.