11beta-hydroxysteroid dehydrogenase 1 and 2 expression in colon from patients with ulcerative colitis.
OBJECTIVE
11beta-hydroxysteroid dehydrogenase (11betaHSD) is an enzyme responsible for the interconversion of active 11beta-hydroxysteroids (cortisol) into biologically inactive 11-oxosteroids (cortisone). The isoform 11betaHSD1 operates predominantly as a reductase converting cortisone to cortisol, whereas 11betaHSD2 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 11betaHSD1 and 11betaHSD2.


METHODS
Quantitative real-time RT-PCR was used to assess messenger RNA for 11betaHSD1 and 11betaHSD2 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 11betaHSD1 mRNA and down-regulated 11betaHSD2 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 11betaHSD1 and impairs glucocorticoid inactivation via 11betaHSD2. The observed changes indicate a role for local metabolism of glucocorticoids in the control of colonic inflammation.
Zbánková
Sárka
S
Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
Bryndová
Jana
J
Leden
Pavel
P
Kment
Milan
M
Svec
Alexander
A
Pácha
Jirí
J
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000096:biosynthesis*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D003093:Colitis, Ulcerative / Q000201:enzymology*; D003106:Colon / Q000201:enzymology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2