Glucocorticoid availability in colonic inflammation of rat
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- 11-beta-Hydroxysteroid Dehydrogenase Type 1 genetics metabolism MeSH
- 11-beta-Hydroxysteroid Dehydrogenase Type 2 genetics metabolism MeSH
- Hormone Antagonists pharmacology MeSH
- Budesonide pharmacology MeSH
- Cyclooxygenase 2 genetics metabolism MeSH
- Glucocorticoids antagonists & inhibitors metabolism pharmacology MeSH
- Interleukin-1beta genetics metabolism MeSH
- Carbenoxolone pharmacology MeSH
- Colitis chemically induced metabolism MeSH
- Colon drug effects enzymology metabolism MeSH
- Corticosterone metabolism MeSH
- Rats MeSH
- Trinitrobenzenesulfonic Acid MeSH
- RNA, Messenger metabolism MeSH
- Mifepristone pharmacology MeSH
- Disease Models, Animal MeSH
- Mucin-2 MeSH
- Mucins genetics metabolism MeSH
- Peroxidase metabolism MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Rats, Wistar MeSH
- Tumor Necrosis Factor-alpha genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 11-beta-Hydroxysteroid Dehydrogenase Type 1 MeSH
- 11-beta-Hydroxysteroid Dehydrogenase Type 2 MeSH
- Hormone Antagonists MeSH
- Budesonide MeSH
- Cyclooxygenase 2 MeSH
- Glucocorticoids MeSH
- Interleukin-1beta MeSH
- Carbenoxolone MeSH
- Corticosterone MeSH
- Trinitrobenzenesulfonic Acid MeSH
- RNA, Messenger MeSH
- Mifepristone MeSH
- Muc2 protein, rat MeSH Browser
- Mucin-2 MeSH
- Mucins MeSH
- Peroxidase MeSH
- Ptgs2 protein, rat MeSH Browser
- Tumor Necrosis Factor-alpha MeSH
Recent in vitro studies have shown the involvement of pro-inflammatory cytokines in the regulation of the local metabolism of glucocorticoids via 11beta-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 alpha (TNF-alpha), and interleukin 1beta (IL-1beta). The metabolism of glucocorticoids was measured in tissue slices in vitro and their 11HSD1, 11HSD2, COX-2, MUC-2, TNF-alpha, and IL-1beta 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-alpha, and IL-1beta, 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-alpha, and IL-1beta in inflamed tissue.
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