Butler CA et al. – Glucocorticoid receptor β (GR Β) mRNA is expressed at low levels in a minority of patients with severe asthma. histone deacetylase 2 (HDAC2) and HDAC2 expression was not downregulated in severe asthma. These data do not support upregulated GR β and resultant reduced HDAC expression as the principal mechanism of steroid resistance in severe asthma. Conflicting GR β literature may be explained in part by clathrin cross–reactivity with commercial antibodies.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–GR β antibody.
- Protein and mRNA expression for GR α and HDAC2 did not differ between groups.
- GR Β 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 GR β antibody detected an additional ‘cross–reacting’ protein, identified as clathrin.
- HDAC1 expression was increased in patients with severe asthma compared with healthy volunteers.