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Vol. 47. Issue 3.
Pages 115-121 (January 2011)
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Vol. 47. Issue 3.
Pages 115-121 (January 2011)
Original Article
DOI: 10.1016/S1579-2129(11)70029-5
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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
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Cristina Embida,??
Corresponding author
cembid@clinic.ub.es

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
Abstract
Background

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.

Methods

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.

Results

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).

Conclusions

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.

Keywords:
Severe asthma
Nasal polyposis
Glucocorticoid receptor
Resumen
Introducción

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.

Métodos

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.

Resultados

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).

Conclusiones

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
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Copyright © 2011. Sociedad Española de Neumología y Cirugía Torácica
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