Article

Regulation of glucocorticoid receptor in nasal polyps by systemic and intranasal glucocorticoids.

Clinical and Experimental Respiratory Immunoallergy, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Allergy (impact factor: 6.27). 10/2008; 63(10):1377-86. DOI:10.1111/j.1398-9995.2008.01745.x pp.1377-86
Source: PubMed

ABSTRACT Poor response of nasal polyps to glucocorticoids (GCs) may be because of abnormal expression of GC receptors (GR) alpha and beta or to downregulation of GRalpha. 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.
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 (10(2) cDNA copies/mug 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.
At w0, nasal polyps expressed less GRalpha 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). GRbeta immunoreactivity was higher in nasal polyps (11;4-19; P < 0.05) than in nasal mucosa (5;2-5). At w2, increased GRalpha 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, GRalpha mRNA and GR protein were similar to w0. GRbeta expression was unaltered by treatment. Neither GRalpha nor GRbeta correlated with nasal symptoms. GR immunoreactivity negatively correlated with eosinophils (r = -0.478; P < 0.001).
GRalpha is downregulated in nasal polyps and upregulated by GC treatment. Neither GRalpha nor GRbeta appear to determine the sensitivity to GCs in nasal polyposis.

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Keywords

% immunoreactive inflammatory cells
 
10 additional weeks
 
abnormal expression
 
GC treatment
 
GC-treated nasal polyps
 
GR levels
 
GR mRNA
 
GR protein
 
GRalpha
 
GRalpha mRNA
 
GRbeta
 
GRbeta correlated
 
GRbeta expression
 
GRbeta immunoreactivity
 
Healthy nasal mucosa
 
intranasal budesonide
 
nasal mucosa
 
nasal polyps
 
nasal symptoms
 
oral prednisone