Expression profiles of human 11beta-hydroxysteroid dehydrogenases type 1 and type 2 in inflammatory bowel diseases.
Inflammatory bowel diseases such as Crohn's disease (CD) and ulcerative colitis (UC) are characterized by an increase in pro-inflammatory cytokines. On the other hand, endogenous cortisol is regarded as physiological compound to combat inflammation. The local activation of glucocorticoids is mediated by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) which increases cortisol, and 11beta-HSD2 which decreases cortisol concentrations. We hypothesized that in inflamed tissues of patients suffering from inflammatory bowel diseases 11beta-HSD1 is upregulated whereas 11beta-HSD2 is downregulated. By using quantitative real-time PCR, we investigated the transcription levels of 11beta-HSD1 and 11beta-HSD2 in patients diagnosed with CD or UC. Expression of 11beta-HSD1 was significantly elevated in inflamed tissue compared to non-inflamed colonic tissue in both, CD (2.7-fold) and UC (3.8-fold), whereas 11beta-HSD2 expression was decreased in the same samples. In both diseases, male patients showed a more pronounced upregulation of 11beta-HSD1 (CD: 4.8-fold, UC: 6.5-fold) compared to females (CD: 1.8-fold, UC: 1.8-fold), a fact which might be due to the higher levels of circulating anti-inflammatory estrogens in women. Our data support the hypothesis that both enzymes play a crucial role in inflammation by affecting local tissue ratios between active and inactive glucocorticoids.
Stegk
J P
JP
Institute of Toxicology and Pharmacology for Natural Scientists, University Medical School Schleswig-Holstein, Brunswiker Strasse 10, Kiel, Germany.
Ebert
B
B
Martin
H-J
HJ
Maser
E
E
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D003093:Colitis, Ulcerative / Q000201:enzymology / Q000235:genetics; D003348:Cortisone / Q000737:chemistry / Q000378:metabolism; D003424:Crohn Disease / Q000201:enzymology / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006854:Hydrocortisone / Q000737:chemistry / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics
D012333:RNA, Messenger; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468386:HSD11B1 protein, human; C468387:HSD11B2 protein, human; D003348:Cortisone; D006854:Hydrocortisone