Publish in this journal
Journal Information
Vol. 47. Issue 3.
Pages 115-121 (January 2011)
Download PDF
More article options
Vol. 47. Issue 3.
Pages 115-121 (January 2011)
Original Article
DOI: 10.1016/S1579-2129(11)70029-5
Full text access
Nuclear Translocation of the Glucocorticoid Receptor in Fibroblasts of Asthmatic Patients with Nasal Polyposis Insensitive to Glucocorticoid Treatment
Translocación nuclear del receptor de glucocorticoides en fibroblastos de pacientes asmáticos con poliposis nasal insensible al tratamiento glucocorticoideo
Cristina Embida,
Corresponding author

Corresponding author.
, Laura Fernández-Bertolínb,d, Laura Pujolsb,d, Isam Alobidb,c,d, Joaquim Mullolb,c,d, César Picadoa,d,e
a Servei de Pneumologia i Al.lèrgia Respiratoria, Hospital Clínic, Barcelona, Spain
b Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
c Servei d’Otorrinolaringologia, Hospital Clínic, Barcelona, Spain
d CIBER de Enfermedades Respiratorias (CIBERES)
e Universitat de Barcelona, Barcelona, Spain
Article information

Nasal polyposis (NP) is treated with topical glucocorticoids (GC). Some patients require endoscopic sinonasal surgery because GC treatment is ineffective. To exert its function, the GC needs to bind with the GC receptor (GR) and the GC-GR complex moves to the cell nucleus. Our aim was to establish whether the poor response to GC is due to an alteration in the translocation of the GR to the nucleus.


Nasal fibroblast cell cultures were made from samples of seven healthy controls and 12 patients with NP and asthma. Fibroblasts were incubated with budesonide or dexamethasone (10?7 M) for different times (30 min to 4 h) and GR translocation was analyzed by immunocytochemistry.


Both GCs induced GR translocation in every group, doubling its concentration in the cell nucleus (30 min) compared to baseline. There were no differences in GR translocation between controls and patients, nor differences related to the severity of asthma or intolerance to non-steroidal anti-inflammatory drugs (NSAIDs). Atopic subjects showed a decrease in GR translocation with budesonide (1 h, 3 h and 4 h, p<0.05) and dexamethasone (30 min and 2 h, P<.05).


The insensitivity to GC treatment does not appear to be due to an alteration in GR translocation to the nucleus. Neither does asthma severity nor intolerance to NSAIDs appear to influence GR translocation. The association between atopy and the alteration in GR translocation merits further investigation.

Severe asthma
Nasal polyposis
Glucocorticoid receptor

La poliposis nasal (PN) se trata con glucorticoides (GC) tópicos. En algunos pacientes el tratamiento es ineficaz requiriéndose cirugía endoscópica nasosinusal. Para ejercer su función, el GC precisa unirse al receptor de GC (RG) y este desplazarse al núcleo celular. Nuestro objetivo fue establecer si la pobre respuesta a los GC es debida a una alteración en la translocación del RG al núcleo.


Se realizaron cultivos celulares de fibroblastos nasales de 7 controles sanos y 12 pacientes con PN y asma. Los fibroblastos se incubaron con budesonida o dexametasona (10?7 M) durante diferentes tiempos (30 min a 4 h) y la translocación del RG se analizó mediante inmunocitoquímica.


Ambos GC indujeron translocación del RG en todos los grupos, doblando su concentración en el núcleo (30 min) respecto al basal. No encontramos diferencias en la translocación del RG entre controles y pacientes ni relación con la gravedad del asma o la intolerancia a los antiinflamatorios no esteroideos (AINE). En los sujetos atópicos se observó una disminución de la translocación con budesonida (1 h, 3 h y 4 h, p<0,05) y dexametasona (30 min y 2 h, p<0,05).


La insensibilidad al tratamiento con GC no parece responder a alteraciones en la translocación del RG al núcleo. Tampoco la gravedad del asma ni la intolerancia a los AINE parecen influir en la translocación del RG. La asociación entre atopía y la alteración en la translocación del RG merece estudiarse más profundamente.

Palabras clave:
Asma grave
Poliposis nasal
Receptor de glucocorticoide
Full text is only aviable in PDF
W. Fokkens, V. Lund, J. Mullol.
European position paper on rhinosinusitis and nasal polyps.
Rhinol, (2007), pp. 1-136
J. Mullol, A. Obando, L. Pujols, I. Alobid.
Corticosteroid treatment in chronic rhinosinusitis: the possibilities and the limits.
Immunol Allergy Clin North Am, 29 (2009), pp. 657-668
C. Kroegel.
[Global Initiative for Asthma Management and Prevention-GINA 2006].
Pneumologie, 61 (2007), pp. 295-304
P.J. Barnes, A.J. Woolcock.
Difficult asthma.
Eur Respir J, 12 (1998), pp. 1209-1218
J. Serra-Batlles, V. Plaza, E. Morejon, A. Comella, J. Brugues.
Costs of asthma according to the degree of severity.
Eur Respir J, 12 (1998), pp. 1322-1326
I.M. Adcock, K. Ito.
Steroid resistance in asthma: a major problem requiring novel solutions or a non-issue?.
Curr Opin Pharmacol, 4 (2004), pp. 257-262
C. Picado.
Aspirin intolerance and nasal polyposis.
Curr Allergy Asthma Rep, 2 (2002), pp. 488-493
L. Pujols, J. Mullol, C. Picado.
Alpha and beta glucocorticoid receptors: relevance in airway diseases.
Curr Allergy Asthma Rep, 7 (2007), pp. 93-99
L. Pujols, J. Mullol, C. Picado.
Importance of glucocorticoid receptors in upper and lower airways.
Front Biosci, 15 (2010), pp. 789-800
M. Beato, M. Truss, S. Chávez.
Control of transcription by steroid hormones.
Ann N Y Acad Sci, 784 (1996), pp. 93-123
L. Pujolsa, J. Mullol, C. Picado.
Glucocorticoid receptor in human respiratory epithelial cells.
Neuroimmunomodulation, 16 (2009), pp. 290-299
P.J. Barnes, I.M. Adcock.
How do corticosteroids work in asthma?.
Ann Intern Med, 139 (2003), pp. 359-370
L. Pujols, I. Alobid, P. Benítez, A. Martínez-Antón, J. Roca-Ferrer, W.J. Fokkens, et al.
Regulation of glucocorticoid receptor in nasal polyps by systemic and intranasal glucocorticoids.
J. Casadevall, P.J. Ventura, J. Mullol, C. Picado.
Intranasal challenge with aspirin in the diagnosis of aspirin intolerant asthma: evaluation of nasal response by acoustic rhinometry.
Thorax, 55 (2000), pp. 921-924
C. Bachert, P. van Cauwenberge, N. Khaltaev.
Allergic rhinitis and its impact on asthma. In collaboration with the World Health Organization. Executive summary of the workshop report. 7–10 December 1999, Geneva, Switzerland.
Allergy, 57 (2002), pp. 841-855
J.H. Krouse, R.W. Brown, S.M. Fineman, J.K. Han, A.J. Heller, S. Joe, et al.
Asthma and the unified airway.
Otolaryngol Head Neck Surg, 136 (2007), pp. S75-S106
O.S. Usmani, K. Ito, K. Maneechotesuwan, M. Ito, M. Johnson, P.J. Barnes, et al.
Glucocorticoid receptor nuclear translocation in airway cells after inhaled combination therapy.
Am J Respir Crit Care Med, 172 (2005), pp. 704-712
E. Goleva, L.B. Li, P.T. Eves, M.J. Strand, R.J. Martin, D.Y. Leung.
Increased glucocorticoid receptor beta alters steroid response in glucocorticoid-insensitive asthma.
Am J Respir Crit Care Med, 173 (2006), pp. 607-616
O. Eickelberg, M. Roth, R. Lorx, V. Bruce, J. Rudiger, M. Johnson, et al.
Ligandindependent activation of the glucocorticoid receptor by beta2-adrenergic receptor agonists in primary human lung fibroblasts and vascular smooth muscle cells.
J Biol Chem, 274 (1999), pp. 1005-1010
E. Catena, G. Mazzarella, G.F. Peluso, P. Micheli, A. Cammarata, S.A. Marsico.
Phenotypic features and secretory pattern of alveolar macrophages in atopic asthmatic patients.
Monaldi Arch Chest Dis, 48 (1993), pp. 6-15
L.W. Poulter, C.M. Burke.
Macrophages and allergic lung disease.
Immunobiology, 195 (1996), pp. 574-587
R.M. Ford.
Etiology of asthma: a continuing review (8071 cases seen from 1970-1980).
Ann Allergy, 50 (1983), pp. 47-50
S.J. Langley, S. Goldthorpe, M. Craven, J. Morris, A. Woodcock, A. Custovic.
Exposure and sensitization to indoor allergens: association with lung function, bronchial reactivity, and exhaled nitric oxide measures in asthma.
J Allergy Clin Immunol, 112 (2003), pp. 362-368
R. Wolfe, J.B. Carlin, H. Oswald, A. Olinsky, P.D. Phelan, C.F. Robertson.
Association between allergy and asthma from childhood to middle adulthood in an Australian cohort study.
Am J Respir Crit Care Med, 162 (2000), pp. 2177-2181
S.R. Nimmagadda, S.J. Szefler, J.D. Spahn, W. Surs, D.Y. Leung.
Allergen exposure decreases glucocorticoid receptor binding affinity and steroid responsiveness in atopic asthmatics.
Am J Respir Crit Care Med, 155 (1997), pp. 87-93
A. Torrego, L. Pujols, J. Roca-Ferrer, J. Mullol, A. Xaubet, C. Picado.
Glucocorticoid receptor isoforms alpha and beta in in vitro cytokine-induced glucocorticoid insensitivity.
Am J Respir Crit Care Med, 170 (2004), pp. 420-425
Copyright © 2011. Sociedad Española de Neumología y Cirugía Torácica
Archivos de Bronconeumología (English Edition)

Subscribe to our newsletter

Article options
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?