Schmidt, Martin and Straub, Rainer H. (2015) 11 beta-Hydroxysteroid Dehydrogenase Enzymes Modulate Effects of Glucocorticoids in Rheumatoid Arthritis Synovial Cells. NEUROIMMUNOMODULATION, 22 (1-2). pp. 40-45. ISSN 1021-7401, 1423-0216
Full text not available from this repository. (Request a copy)Abstract
The tissue availability of active glucocorticoids (cortisol in humans) depends on their rate of synthesis from cholesterol, downstream metabolism, excretion and interconversion. The latter is mediated by the 11 beta-hydroxysteroid dehydrogenases (11 beta HSDs). In this review, we summarize the features of the two isoenzynnes, 11 beta HSD1 and 11 beta HSD2, and current available experimental data related to 11 beta HSDs, which are relevant in the context of synovial cells in rheumatoid arthritis (RA). We conclude that due to complex feedback mechanisms inherent to the hypothalamic-pituitary-adrenal axis, currently available transgenic animal models cannot display the full potential otherwise inherent to the techniques. Studies with tissue explants, mixed synovial cell preparations, cell lines derived from synovial cells, and related primary cells or established cell lines indicate that there are relatively clear differences between the two isoenzymes. 11 beta HSD1 is expressed primarily in fibroblasts and osteoblasts, and may be responsible for fibroblast survival and aid in the resolution of inflammation, but it is also involved in bone damage. 11 beta HSD2 is expressed primarily in macrophages and lymphocytes, and may be responsible for their survival, suggesting that it is critical in chronic inflammation. The situation in synovial tissue would allow 11 beta HSD2-expressing cells to tap the energy resources of 11 beta HSD1-expressing cells. The overall properties of this local glucocorticoid interconversion system might limit therapeutic use of glucocorticoids in RA. (C) 2014 S. Karger AG, Basel
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFLAMMATORY ARTHRITIS; GENE-EXPRESSION; IN-VIVO; METABOLISM; TYPE-1; OSTEOBLASTS; MACROPHAGES; INHIBITORS; CORTISONE; DISEASE; Rheumatoid arthritis; Glucocorticoid receptor; 11 beta-Hydroxysteroid dehydrogenases |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Aug 2019 08:01 |
| Last Modified: | 05 Aug 2019 08:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/6395 |
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