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11-beta hydroxysteroid dehydrogenase 1 and 2 expression in colon from patients with ulcerative colitis

Publikace na 3. lékařská fakulta |
2007

Tento text není v aktuálním jazyce dostupný. Zobrazuje se verze "en".Abstrakt

Background and Aim: 11β-hydroxysteroid dehydrogenase (11βHSD) is an enzyme responsible for the interconversion of active 11β-hydroxysteroids (cortisol) into biologically inactive 11-oxosteroids (cortisone). The isoform 11βHSD1 operates predominantly as a reductase converting cortisone to cortisol, whereas 11βHSD2 catalyzes oxidation of cortisol to cortisone.

This mechanism of peripheral metabolism of glucocorticoids has been suggested to be involved in increasing the availability of anti- inflammatory glucocorticoids as a response to inflammatory stimuli. The aim of this study therefore was to investigate the impact of inflammatory bowel disease on the expression of colonic 11βHSD1 and 11βHSD2.

Methods: Quantitative real-time RT-PCR was used to assess messenger RNA for 11βHSD1 and 11βHSD2 in bioptic samples taken from patients with ulcerative colitis and in healthy controls, and in colon of rats with colitis induced by dextran sulfate sodium (DSS). Rat colonic fragments were used for assessment of local metabolism of glucocorticoids.

Results: In both human and rat specimens colitis up-regulated the expression of colonic 11βHSD1 mRNA and down-regulated 11βHSD2 mRNA. A similar pattern was observed at the level of local metabolism of corticosterone.

Oxidation of corticosterone to 11-dehydrocorticosterone was decreased and reduction of 11-dehydrocorticosterone to corticosterone was increased in colonic tissue of rats with DSS-colitis. Conclusions: Colonic inflammation induces local glucocorticoid activation via 11βHSD1 and impairs glucocorticoid inactivation via 11βHSD2.

The observed changes indicate a role for local metabolism of glucocorticoids in the control of colonic inflammation.