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.
About the authors
Sabine Hübner studied Biology at the University of Jena in Germany. She undertook her PhD about tissue-specific hormone-action in the group of Jan Tuckermann at the Fritz Lipmann Institute for Age Reseach in Jena, Germany. In April 2013 she became a postdoctoral researcher at the university of Ulm in the Institute for Comparative Molecular Endocrinology. She is interested in glucocorticoid action in inflammation and metabolism.
Lien Dejager finished her PhD in Biotechnology from the University of Ghent in 2010 under the guidance of Prof. Claude Libert, IRC, VIB. After that she became a postdoctoral researcher at FWO-Vlaanderen in the same group. In 2014, she did a research stay in the lab of Prof Jan Tuckermann, University of Ulm. Her major research interests are elucidating the anti-inflammatory mechanisms of glucocorticoids and the mechanisms underlying glucocorticoid resistance, aiming to design more efficient glucocorticoid-based therapies.
Claude Libert (1964) has a Masters degree and PhD in Sciences, both obtained at the University of Ghent under the guidance of Walter Fiers. After a postdoc in Italy, he became a group leader with VIB (Flanders Institute for Biotechnology) in 1997 and a professor at the University of Ghent in 2003. His major research interest is acute inflammation and the cross-talk between several important players in inflammation, with a focus on TNF, IFN, matrix metalloproteinases and glucocorticoids.
Jan P. Tuckermann studied Biology and performed his graduate studies in the labs of Peter Herrlich (Karlsruhe, Germany) and Peter Angel (Heidelberg, Germany) and his postdoc with Günther Schütz (Heidelberg, Germany). He then worked as a group leader at the Fritz LIpmann Institute (Jena, Germany) and was appointed in 2012 as a full professor to head the Institute of Comparative Molecular Endocrinology at the University of Ulm (Germany). Dr. Tuckermann made major contributions to the molecular mechanisms of corticosteroids in beneficial and side-effects of steroid therapy. With the help of conditional and function selective knockout mice for the glucocorticoid receptor (GR) he identified the critical cell types for anti-inflammatory activities of glucocorticoids in different inflammatory disease models. A second focus of his work concerns the effects of glucocorticoids on bone integrity, as glucocorticoid-induced osteoporosis which is a major side effect of long-term corticosteroid therapy.
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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