ECTS2014 Poster Presentations Steroid hormones and receptors (4 abstracts)
Glucocorticoids suppress inflammation in arthritis via the glucocorticoid receptor in non-hematopoietic cells
Ulrike Baschant 1, , Stephan Culemann 3 , Mascha Koenen 1 , Hong Zhou 4 , Markus Seibel 4 , Lorenz Hofbauer 2 & Jan Tuckermann 1
1Institute of General Zoology and Endocrinology, University Ulm, Ulm, Germany; 2Division of Endocrinology, Diabetes and Bone Diseases, TU Medical Center Dresden, Dresden, Germany; 3Institute of Rheumatology and Immunology, University of Erlangen, Erlangen, Germany; 4ANZAC Research Institute, University of Sydney, Sydney, Australia.
Owing to their anti-inflammatory effects, steroid therapy using glucocorticoids (GCs) is still part of the treatment of rheumatoid arthritis (RA), despite several severe side effects like glucocorticoid-induced osteoporosis (GIO). Until now the molecular mechanisms underlying the beneficial and side effects of GC therapy are poorly understood. GCs exert their actions via the glucocorticoid receptor (GR) that alters gene expression by either binding as a dimer to GC response elements in the promoter region of target genes or by interacting with and thus interfering with other transcription factors.
Using conditional and functional GR mutant mice, we previously showed in antigen-induced arthritis (AIA) that GCs reduce acute inflammation via the dimerized GR in IL17 producing T cells (PNAS 2011, 108:19317).
Now, we demonstrate that in the chronic, bone destructive K/BxN serum transfer induced arthritis, a T cell independent model of arthritis, unexpectedly, dimerization of the GR in non-hematopoietic cells contributes to the anti-inflammatory effect of GCs. Currently we test, which type of mesenchymal cells mediate the immunosuppressive effects of glucocorticoids in arthritis. Thus, for immunosuppression of arthritis GR dimer dependent gene regulation is decisive in distinct cell types, partly of non-hematopoietic origin. Our findings of GC action in arthritis have consequences on new concepts for anti-inflammatory therapies.
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