Digestive Diseases and Sciences

, Volume 53, Issue 8, pp 2160–2167 | Cite as

Glucocorticoid Availability in Colonic Inflammation of Rat

  • P. Ergang
  • P. Leden
  • J. Bryndová
  • Š. Žbánková
  • I. Mikšík
  • M. Kment
  • J. Pácha
Original Paper


Recent in vitro studies have shown the involvement of pro-inflammatory cytokines in the regulation of the local metabolism of glucocorticoids via 11β-hydroxysteroid dehydrogenase type 1 and type 2 (11HSD1 and 11HSD2). However, direct in vivo evidence for a relationship among the local metabolism of glucocorticoids, inflammation and steroid enzymes is still lacking. We have therefore examined the changes in the local metabolism of glucocorticoids during colonic inflammation induced by TNBS and the consequences of corticosterone metabolism inhibition by carbenoxolone on 11HSD1, 11HSD2, cyclooxygenase 2 (COX-2), mucin 2 (MUC-2), tumor necrosis factor α (TNF-α), and interleukin 1β (IL-1β). The metabolism of glucocorticoids was measured in tissue slices in vitro and their 11HSD1, 11HSD2, COX-2, MUC-2, TNF-α, and IL-1β mRNA abundances by quantitative reverse transcription-polymerase chain reaction. Colitis produced an up-regulation of colonic 11HSD1 and down-regulation of 11HSD2 in a dose-dependent manner, and these changes resulted in a decreased capacity of the inflamed tissue to inactivate tissue corticosterone. Similarly, 11HSD1 transcript was increased in colonic intraepithelial lymphocytes of TNBS-treated rats. Topical intracolonic application of carbenoxolone stimulated 11HSD1 mRNA and partially inhibited 11HSD2 mRNA and tissue corticosterone inactivation and these changes were blocked by RU-486. The administration of budesonide mimicked the effect of carbenoxolone. In contrast to the local metabolism of glucocorticoids, carbenoxolone neither potentiates nor diminishes gene expression for COX-2, TNF-α, and IL-1β, despite the fact that budesonide down-regulated all of them. These data indicate that inflammation is associated with the down-regulation of tissue glucocorticoid catabolism. However, these changes in the local metabolism of glucocorticoids do not modulate the expression of COX-2, TNF-α, and IL-1β in inflamed tissue.


11β-hydroxysteroid dehydrogenase Inflammation TNBS-colitis 



This study was supported by the Ministry of Health (grant NR/8576–3), the Czech Science Foundation (305/07/0328) and Charles University (grant no. 77/2006 C). The authors are grateful to Mrs. I. Mezteková for technical assistance.


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • P. Ergang
    • 1
  • P. Leden
    • 1
    • 2
  • J. Bryndová
    • 1
  • Š. Žbánková
    • 1
    • 2
  • I. Mikšík
    • 1
  • M. Kment
    • 2
  • J. Pácha
    • 1
  1. 1.Institute of PhysiologyCzech Academy of SciencesPrague 4-KrčThe Czech Republic
  2. 2.Department of Medicine, Third Faculty of MedicineCharles UniversityPragueThe Czech Republic

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