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The Role and Regulation of the 11 Beta-Hydroxysteroid Dehydrogenase Enzyme System in Patients with Inflammatory Bowel Disease.

Authors
  • Hussey, M1, 2
  • Holleran, G3
  • Smith, S3
  • Sherlock, Mark4
  • McNamara, D5, 3
  • 1 Department of Gastroenterology, Adelaide and Meath Hospital, Tallaght, Dublin 24, Ireland. [email protected] , (Ireland)
  • 2 Trinity Academic Gastroenterology Group, Trinity College Dublin, Dublin, Ireland. [email protected] , (Ireland)
  • 3 Trinity Academic Gastroenterology Group, Trinity College Dublin, Dublin, Ireland. , (Ireland)
  • 4 Department of Endocrinology, Adelaide and Meath Hospital, Tallaght, Dublin 24, Ireland. , (Ireland)
  • 5 Department of Gastroenterology, Adelaide and Meath Hospital, Tallaght, Dublin 24, Ireland. , (Ireland)
Type
Published Article
Journal
Digestive Diseases and Sciences
Publisher
Springer-Verlag
Publication Date
Dec 01, 2017
Volume
62
Issue
12
Pages
3385–3390
Identifiers
DOI: 10.1007/s10620-017-4753-1
PMID: 28932959
Source
Medline
Keywords
License
Unknown

Abstract

Results have demonstrated a significant downregulation in 11β-HSD2 expression in IBD patients compared with controls (13.8 ± 17.1 au vs. 318.4 ± 521.1 au, p = 0.01), whereas levels of 11β-HSD1 did not appear to vary across the two groups. Among IBD patients, there was a trend toward higher 11β-HSD1 expression in inflamed tissue compared with matched non-inflamed tissue (422.1 ± 944 au vs. 102.2 ± 103.9, P = 0.09). Levels of H6PDH and the GR-α expression did not appear to vary among active inflamed IBD tissue and controls. As a result, we examined the association between pro-inflammatory cytokines and levels of 11β-HSD2 expression. Results showed an upregulation of key pro-inflammatory cytokine mRNA expression (TNF-α, IL-1β, IL-6) during inflammation with an associated downregulation of 11β-HSD2 mRNA expression when compared to controls. Dysregulation in this pathway could have a potential role in IBD pathogenesis and may account for exogenous glucocorticoid resistance in IBD. Further work assessing the role of the 11β-HSD enzyme system in steroid-resistant subjects is warranted.

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