Journal
BIOLOGICAL CHEMISTRY
Volume 396, Issue 11, Pages 1223-1231Publisher
WALTER DE GRUYTER GMBH
DOI: 10.1515/hsz-2015-0106
Keywords
ChIP-Seq; glucocorticoid receptor; inflammation; transactivation; transgenic mice; transrepression
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Funding
- Deutsche Forschungsgemeinschaft 'Immunobone', Collaborative Research Centre 1149 from KaroBioScience Foundation [SPP 1468 Tu220/6-2]
- EU FP7 Programme BRAINAGE
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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.
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