Hardy, RS, Filer, A, Cooper, MS et al. (7 more authors) (2006) Differential expression, function and response to inflammatory stimuli of 11β-hydroxysteroid dehydrogenase type 1 in human fibroblasts: a mechanism for tissue-specific regulation of inflammation. Arthritis Research and Therapy, 8 (4). ARTN R108. ISSN 1478-6354
Abstract
Stromal cells such as fibroblasts play an important role in defining tissue-specific responses during the resolution of inflammation. We hypothesized that this involves tissue-specific regulation of glucocorticoids, mediated via differential regulation of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Expression, activity and function of 11β-HSD1 was assessed in matched fibroblasts derived from various tissues (synovium, bone marrow and skin) obtained from patients with rheumatoid arthritis or osteoarthritis. 11β-HSD1 was expressed in fibroblasts from all tissues but mRNA levels and enzyme activity were higher in synovial fibroblasts (2-fold and 13-fold higher mRNA levels in dermal and synovial fibroblasts, respectively, relative to bone marrow). Expression and activity of the enzyme increased in all fibroblasts following treatment with tumour necrosis factor-β or IL-1β (bone marrow: 8-fold and 37-fold, respectively, compared to vehicle; dermal fibroblasts: 4 fold and 14-fold; synovial fibroblasts: 7-fold and 31-fold; all P < 0.01 compared with vehicle). Treatment with IL-4 or interferon-β was without effect, and there was no difference in 11β-HSD1 expression between fibroblasts (from any site) obtained from patients with rheumatoid arthritis or osteoarthritis. In the presence of 100 nmol/l cortisone, IL-6 production - a characteristic feature of synovial derived fibroblasts - was significantly reduced in synovial but not dermal or bone marrow fibroblasts. This was prevented by co-treatment with an 11β-HSD inhibitor, emphasizing the potential for autocrine activation of glucocorticoids in synovial fibroblasts. These data indicate that differences in fibroblast-derived glucocorticoid production (via the enzyme 11β-HSD1) between cells from distinct anatomical locations may play a key role in the predeliction of certain tissues to develop persistent inflammation.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2006, Hardy, RS, Filer, A, Cooper, MS, Parsonage, G, Raza, K, Hardie, DL, Rabbitt, EH, Stewart, PM, Buckley, CD and Hewison, M. This is an Open Access article distributed in accordance with the Creative Commons Attribution (CC BY 2.0) licence, which permits others to distribute, remix, adapt, build upon this work, and license their derivative works on different terms, provided the original work is properly cited. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Medicine & Health Faculty Office (Leeds) > Faculty Office Functions (FOMH) (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 04 Nov 2014 12:35 |
Last Modified: | 06 Nov 2017 04:43 |
Published Version: | http://dx.doi.org/10.1186/ar1993 |
Status: | Published |
Publisher: | BioMed Central |
Identification Number: | 10.1186/ar1993 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:81075 |