Stegk J P, Ebert B, Martin H-J, Maser E
Institute of Toxicology and Pharmacology for Natural Scientists, University Medical School Schleswig-Holstein, Brunswiker Strasse 10, Kiel, Germany.
Mol Cell Endocrinol. 2009 Mar 25;301(1-2):104-8. doi: 10.1016/j.mce.2008.10.030. Epub 2008 Oct 31.
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.
克罗恩病（CD）和溃疡性结肠炎（UC）等炎症性肠病的特征是促炎细胞因子增加。另一方面，内源性皮质醇被视为对抗炎症的生理化合物。糖皮质激素的局部激活由11β-羟基类固醇脱氢酶1型（11β-HSD1）介导，其可增加皮质醇水平，还有11β-羟基类固醇脱氢酶2型（11β-HSD2），其可降低皮质醇浓度。我们推测，在炎症性肠病患者的炎症组织中，11β-HSD1上调，而11β-HSD2下调。通过定量实时PCR，我们研究了诊断为CD或UC的患者中11β-HSD1和11β-HSD2的转录水平。与非炎症性结肠组织相比，在CD（2.7倍）和UC（3.8倍）中，炎症组织中11β-HSD1的表达均显著升高，而相同样本中11β-HSD2的表达则降低。在这两种疾病中，男性患者的11β-HSD1上调比女性更明显（CD：4.8倍，UC：6.5倍），而女性为（CD：1.8倍，UC：1.8倍），这可能是由于女性循环中抗炎雌激素水平较高。我们的数据支持这样的假设，即这两种酶通过影响活性和非活性糖皮质激素之间的局部组织比例在炎症中起关键作用。
