Glucocorticoid receptor ß and histone deacetylase 1 and 2 expression in the airways of severe asthma.
Thorax
; 67(5): 392-8, 2012 May.
Article
em En
| MEDLINE
| ID: mdl-22156779
ABSTRACT
RATIONALE Upregulation of glucocorticoid receptor ß (GRß) has been implicated in steroid resistance in severe asthma, although previous studies are conflicting. GRß has been proposed as a dominant negative isoform of glucocorticoid receptor α (GRα) but it has also been suggested that GRß can cause steroid resistance via reduced expression of histone deacetylase 2 (HDAC2), a key regulator of steroid responsiveness in the airway. OBJECTIVES:
To examine GRß, GRα, HDAC1 and HDAC2 expression at transcript and protein levels in bronchial biopsies from a large series of patients with severe asthma, and to compare the findings with those of patients with mild to moderate asthma and healthy volunteers.METHODS:
Bronchoscopic study in two UK centres with real-time PCR and immunohistochemistry performed on biopsies, western blotting of bronchial epithelial cells and immunoprecipitation with anti-GRß antibody. MEASUREMENTS AND MAINRESULTS:
Protein and mRNA expression for GRα and HDAC2 did not differ between groups. GRß mRNA was detected in only 13 of 73 samples (seven patients with severe asthma), however immunohistochemistry showed widespread epithelial staining in all groups. Western blotting of bronchial epithelial cells with GRß antibody detected an additional 'cross-reacting' protein, identified as clathrin. HDAC1 expression was increased in patients with severe asthma compared with healthy volunteers.CONCLUSIONS:
GRß mRNA is expressed at low levels in a minority of patients with severe asthma. HDAC1 and HDAC2 expression was not downregulated in severe asthma. These data do not support upregulated GRß and resultant reduced HDAC expression as the principal mechanism of steroid resistance in severe asthma. Conflicting GRß literature may be explained in part by clathrin cross-reactivity with commercial antibodies.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Asma
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Brônquios
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RNA Mensageiro
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Receptores de Glucocorticoides
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Mucosa Respiratória
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Histona Desacetilase 1
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Histona Desacetilase 2
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article