J. Mullol and C. Picado contributed equally to this work with senior responsibilities.
Regulation of glucocorticoid receptor in nasal polyps by systemic and intranasal glucocorticoids
Article first published online: 29 JUL 2008
© 2008 The Authors. Journal compilation © 2008 Blackwell Munksgaard
Volume 63, Issue 10, pages 1377–1386, October 2008
How to Cite
Pujols, L., Alobid, I., Benítez, P., Martínez-Antón, A., Roca-Ferrer, J., Fokkens, W. J., Mullol, J. and Picado, C. (2008), Regulation of glucocorticoid receptor in nasal polyps by systemic and intranasal glucocorticoids. Allergy, 63: 1377–1386. doi: 10.1111/j.1398-9995.2008.01745.x
- Issue published online: 8 SEP 2008
- Article first published online: 29 JUL 2008
- Accepted for publication 11 March 2008
- glucocorticoid receptor;
- glucocorticoid therapy;
- nasal inflammation;
- nasal mucosa;
- nasal polyps
Background: Poor response of nasal polyps to glucocorticoids (GCs) may be because of abnormal expression of GC receptors (GR) α and β or to downregulation of GRα. We aimed to evaluate the in vivo regulation of GR isoforms in GC-treated nasal polyps and to assess the relationship between clinical response to GCs and GR levels.
Methods: Patients with nasal polyps were randomly (3:1) treated (n = 51) or not (n = 14) with oral prednisone and intranasal budesonide for 2 weeks, plus intranasal budesonide for 10 additional weeks. Nasal symptoms were evaluated. Biopsies were obtained before (w0) and after 2 (w2) and 12 (w12) weeks of treatment, and analysed for their inflammatory content and GR mRNA (102 cDNA copies/μg total RNA) and protein (% immunoreactive inflammatory cells) expression. Healthy nasal mucosa (n = 11) was also investigated. Data are presented as median and 25–75th percentile.
Results: At w0, nasal polyps expressed less GRα mRNA (1343;683–2263; P < 0.05) and GR protein (41;29–54; P < 0.05) than nasal mucosa (2474;1346–2933; 60;51–72, respectively). GRβ immunoreactivity was higher in nasal polyps (11;4–19; P < 0.05) than in nasal mucosa (5;2–5). At w2, increased GRα mRNA (2010;1037–2732; P < 0.01) and GR protein (56;27–71; P = 0.056) were found compared with w0 (1177;759–2058; 37;29–55, respectively). At w12, GRα mRNA and GR protein were similar to w0. GRβ expression was unaltered by treatment. Neither GRα nor GRβ correlated with nasal symptoms. GR immunoreactivity negatively correlated with eosinophils (r = −0.478; P < 0.001).
Conclusions: GRα is downregulated in nasal polyps and upregulated by GC treatment. Neither GRα nor GRβ appear to determine the sensitivity to GCs in nasal polyposis.