SFEBES2008 Poster Presentations Steroids (35 abstracts)
Differential effects of glucocorticoids on fibroblasts: mechanisms underlying the adverse features of Cushing’s
Rowan Hardy 1 , Dona Augustine 1 , Kirren Kaur 1 , Ana Slabbert 1 , Karim Raza 2 , Chris Buckley 2 , Paul Stewart 1 , Elizabeth Rabbitt 1 & Mark Cooper 1
1Division of Medicine and 2Division of Rheumatology, The University of Birmingham, Birmingham, West Midlands, UK.
High dose glucocorticoids are effective in suppressing inflammatory synovitis but have adverse effects on other connective tissues. In inflammatory arthritis glucocorticoids suppress the capacity of synovial fibroblasts (SFs) to recruit leukocytes to the joint whereas poor skin healing is due to impaired dermal fibroblast (DF) function. It is unknown whether these clinical differences are due to similar or distinct effects of glucocorticoids on fibroblast function.
We therefore examined the effects of glucocorticoids on proliferation, differentiation and apoptosis in matched primary cultures of synovial and dermal fibroblasts generated from synovium and skin obtained from patients undergoing joint replacement surgery (n=4). Treatment with either 100 nM dexamethasone (DEX) or cortisol inhibited proliferation of DFs in both tritiated thymidine and FACS cell-cycle assays (e.g. 48±12% (mean±S.D.) decrease by tritiated thymidine; P<0.01). By contrast, proliferation of SFs was stimulated by glucocorticoids in both assays (29±13% increased cell number; P<0.01). Glucocorticoids substantially inhibited the expression of inflammatory genes (e.g. COX-2) in SFs but had little effect in DFs (mRNA expression decreased by 52% for SFs (P<0.01), but only 10% for DFs (NS)). Glucocorticoids decreased expression of type 1 collagen to a similar degree (59% with SFs (P<0.01), 54% with DFs). There was no difference in sensitivity to apoptosis as determined by MTT assay.
Fibroblasts from different tissues respond differently to glucocorticoid excess. The reduction in inflammatory gene expression in SFs is likely to be important in the beneficial effects of glucocorticoids in inflammatory arthritis whereas the reduced proliferation of DFs and decreased collagen formation are likely to account for the poor healing of skin in Cushing’s.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more