Accessible Requires Authentication Published by De Gruyter April 23, 2015

The glucocorticoid receptor in inflammatory processes: transrepression is not enough

Sabine Hübner, Lien Dejager, Claude Libert and Jan P. Tuckermann
From the journal Biological Chemistry

Abstract

Glucocorticoids (GCs) are the most commonly used anti-inflammatory agents to treat inflammatory and immune diseases. However, steroid therapies are accompanied by severe side-effects during long-term treatment. The dogma that transrepression of genes, by tethering of the glucocorticoid receptor (GR) to DNA-bound pro-inflammatory transcription factors, is the main anti-inflammatory mechanism, is now challenged. Recent discoveries using conditional GR mutant mice and genomic approaches reveal that transactivation of anti-inflammatory acting genes is essential to suppress many inflammatory disease models. This novel view radically changes the concept to design selective acting GR ligands with a reduced side-effect profile.


Corresponding author: Jan P. Tuckermann, Institute for Comparative Molecular Endocrinology (CME), University of Ulm, Helmholtzstrasse 8/1, 89075 Ulm, Germany, e-mail:
aThese authors contributed equally to this work.

Acknowledgments

JT acknowledges support from Deutsche Forschungsgemeinschaft ‘Immunobone’ (SPP 1468 Tu220/6–2, Collaborative Research Centre 1149) from KaroBioScience Foundation and the EU FP7 Programme BRAINAGE.

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Received: 2015-1-15
Accepted: 2015-4-13
Published Online: 2015-4-23
Published in Print: 2015-11-1

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