Thorax doi:10.1136/thoraxjnl-2011-200760
  • Asthma
  • Original article

Glucocorticoid receptor β and histone deacetylase 1 and 2 expression in the airways of severe asthma

  1. Liam G Heaney1,4
  1. 1Centre for Infection and immunity, Health Sciences Building, Queens University Belfast, Belfast, UK
  2. 2Tissue Pathology, Belfast Health and Social Care Trust, Belfast, UK
  3. 3Department of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences Building, Leicester, UK
  4. 4ITGR Biomarker Discovery, Genentech, Inc., South San Francisco, California, USA
  1. Correspondence to Dr Liam Heaney, Centre for Infection and Immunity, Queens University Belfast, Level 8, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, Northern Ireland, UK; l.heaney{at}
  1. Contributors CB and SMcQ performed immunostaining in the Belfast cohort, analysed the data and contributed to the writing of the manuscript. DC and JA performed and analysed the gene expression data, analysed the data and contributed to the writing of the manuscript. CB and LH recruited subjects, performed bronchoscopy and acquired the demographic data for the Belfast cohort and PB recruited subjects, performed bronchoscopy and acquired the demographic data for the Leicester cohort. TJW and LMcG assisted with bronchoscopy in the Belfast cohort. RC undertook immunohistochemistry for the Leicester cohort and assisted with data analysis under the supervision of PB. CT and SW performed the clathrin western blots and immunostaining. LH and GS conceived and designed the research, contributed to data analysis and interpretation, drafted the original manuscript and supervised CB. All authors approved the final manuscript.

  • Received 7 July 2011
  • Accepted 11 November 2011
  • Published Online First 8 December 2011


Rationale Upregulation of glucocorticoid receptor β (GRβ) has been implicated in steroid resistance in severe asthma, although previous studies are conflicting. GRβ has been proposed as a dominant negative isoform of glucocorticoid receptor α (GRα) but it has also been suggested that GRβ can cause steroid resistance via reduced expression of histone deacetylase 2 (HDAC2), a key regulator of steroid responsiveness in the airway.

Objectives To examine GRβ, 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-GRβ antibody.

Measurements and main results Protein and mRNA expression for GRα and HDAC2 did not differ between groups. GRβ 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 GRβ antibody detected an additional ‘cross-reacting’ protein, identified as clathrin. HDAC1 expression was increased in patients with severe asthma compared with healthy volunteers.

Conclusions GRβ 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 GRβ and resultant reduced HDAC expression as the principal mechanism of steroid resistance in severe asthma. Conflicting GRβ literature may be explained in part by clathrin cross-reactivity with commercial antibodies.


  • Funding CB was supported by a grant from the Northern Ireland Chest, Heart and Stroke Association (reference no. 200645). Research in Leicester was conducted in laboratories and was part funded by ERDF #05567 and supported by a grant-in-aid from Genentech Inc., South San Francisco, California, USA.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

No Related Web Pages

Relevant Article

Free sample
This recent issue is free to all users to allow everyone the opportunity to see the full scope and typical content of Thorax.
View free sample issue >>

Don't forget to sign up for content alerts so you keep up to date with all the articles as they are published.

Navigate This Article