ResearchNEWs & EVENTs
Biologisches Kolloquium 23.05.2012: 17:00 OE/N25 H8
Prof. Dr. Claude Libert
Ghent University and VIBMouse Genetics in Inflammation, Ghent, Belgium
"GR dimers control JNK-mediated inflammation and cell-death via MKP-1 in an in vivo TNF model"
Glucocorticoids (GCs) are very powerful anti-inflammatory agents that function by binding on the GC receptor (GR), which is a member of the nuclear receptor family of proteins. Despite GCs are very widely used in the combat against inflammatory diseases, several problems with GCs/GR are recognized. The problem relevant to this seminar deals with the mechanism by which GR exerts its anti-inflammatory function. After binding of GCs to GR and after nuclear transport, GR can interact with inflammatory transcription factors (such as NFkB), leading to transrepression, but GR can also dimerize and bind on DNA and induce and repress gene expression, in a process called transactivation. The relative contribution of these two processes is still poorly understood. In light of the anti-cancer effects of the cytokine TNF and of its role in numerous inflammatory diseases (anti-TNF therapies belong to the top-10 best selling drugs worldwide), we are studying the GR dimerization in relation to TNF’s inflammation. Using mice expressing a GR pointmutation, leading to a GR that can hardly dimerize, we have found that GR dimerization is essential in the protection of mice against TNF’s toxicity. The extreme TNF sensitivity of such GRdim/dim mice is very comparable to the TNF sensitive phenotype of Dusp1-/- mice. Dusp1 is a gene induced by GR and encoding the major MAP kinase de-phosphorylating phosphatase MKP-1. In the TNF model, Dusp1-/- mice are unable to reverse the phosphorylation of JNK, a phenotype we also observe in GRdim/dim mice. We found that JNK2-/- mice resist TNF toxicity and that Dusp1/JNK2 --/-- mice are less sensitive to TNF compared to Dusp1-/- mice. Since we found that GRdim/dim/JNK2-/- mice are also protected compared to GRdim/dim mice, we believe that GR dimerization is essential in the induction of MKP-1, which in turn controls JNK2 phosphorylation and hence TNF-inuduced, JNK2-mediated inflammation and cell death. Since Dusp1 is not the only GR dimer-induced anti-inflammatory gene, we also focused on the gene Tsc22d3, which encodes GILZ, another such anti-inflammatory gene. I will also show data dealing with the identification of GILZ as an important protective factor in acute inflammation.
Biologisches Kolloquium 17.04.2012: 17:00 OE/N25 H8
Dr. Maja Vujic
Molecular Medicine Partnership Unit, Iron Homeostasis, Univeristätsklinikum Heidelberg, Germany
"Novel roles for Hfe and Hepcidin in metabolism"
#20120401
Since April 1st, 2012 
Prof. Dr. Jan Peter Tuckermann is head of the Institute (Succession of Prof. Dr. Klaus-Dieter Spindler).