Ahmed, A. , Schwaderer, J., Hantusch, A., Kolho, K.-L. and Brunner, T. (2019) Intestinal glucocorticoid synthesis enzymes in pediatric inflammatory bowel disease patients. Genes and Immunity, 20(7), pp. 566-576. (doi: 10.1038/s41435-019-0056-1) (PMID:30686824)
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Abstract
Inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis are devastating chronic immunopathologies of the intestinal mucosa, which are frequently treated by immunosuppressive glucocorticoids. Endogenous glucocorticoids are not only produced by the adrenal glands, but also by the intestinal epithelium. Local glucocorticoid synthesis critically contributes to the immune homeostasis of the intestinal mucosa. As defective intestinal glucocorticoid synthesis has been associated with the development of IBD, we investigated the expression of steroidogenic enzymes and the key transcriptional regulator Liver Receptor Homolog-1 (LRH-1/NR5A2) in ileal and colonic biopsies human pediatric IBD and control patients. Furthermore, the induction of steroidogenic enzymes and their transcriptional regulation by LRH-1 was investigated in a mouse model of experimental colitis. These analyses revealed that colitis-induced expression of steroidogenic enzymes in the murine colon is dependent on the presence of LRH-1, as intestinal deletion of LRH-1 strongly reduced their colitis-induced expression. Similarly, a strong correlation between the expression of LRH-1 and different steroidogenic enzymes was seen in intestinal biopsies of human pediatric patients. Importantly, reduced expression of hydroxysteroid dehydrogenase 11B1 (HSD11B1) was observed in IBD patients compared to control patients, suggesting that defective local reactivation of glucocorticoids could contribute to the pathogenesis of IBD.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported in part by research grants from German Science Foundation to TB, and Pediatric Research Foundation, Finland, and Helsinki University Hospital Research Fund, Finland to KLK. AA was supported by a fellowship from the Ministry of Higher Education and Scientific Research, Sudan and the Baden- Württemberg-Stiftung. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Ahmed Hassan Elshiekh, Dr Asma |
| Authors: | Ahmed, A., Schwaderer, J., Hantusch, A., Kolho, K.-L., and Brunner, T. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Genes and Immunity |
| Publisher: | Nature Research |
| ISSN: | 1466-4879 |
| ISSN (Online): | 1476-5470 |
| Published Online: | 28 January 2019 |
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