SFB 542:  Molecular Mechanisms of Cytokine-Mediated Inflammatory Processes: Signal Transduction and Pathophysiological Consequences

• Subject Area: Medicine ; Biology
• Term: from 1999 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5483639

Besides immuno-competent cells such as monocytes, macrophages, granulocytes and lymphocytes cells of inflamed tissues (endothelial cells, fibroblasts, keratinocytes, hepatocytes, hepatic stellate cells, mensangial cells or glial cells) are involved in the inflammatory response of the organism after infection and injury. The communication between these cells is brought about by cytokines. These polypeptide-mediators act through specific receptors on the surface of target cells. The molecular mechanisms by which these signals are transduced into the cell are not fully understood. The cellular responses range from altered gene expression, proliferation, differentiation, apoptosis, migration to degranulation. Dysregulation of signal transduction cascades and cytokine or receptor expression has been found to be the cause of several diseases. Due to these clinical implications, many academic and commercial research institutions are interested in cytokine-induced signal transduction cascades. The participating members of the collaborative research centre 542 are investigating the role of cytokine action in inflammatory diseases in order to understand their role in pathology. The results of these studies will serve as a rational basis for the development of new diagnostic tools and therapies for acute and chronic inflammatory diseases.

• DFG Programme: Collaborative Research Centres

Completed projects

• A1 - Strukturaufklärung der gp130-Extrazellulärdomänen und des SOCS-1-Proteins mit Hilfe der NMR-Spektroskopie (Project Head Grötzinger, Joachim )
• A02 - Fused soluble receptors as highly potent cytokine inhibitors (Project Head Müller-Newen, Gerhard )
• A3 - Intrazellulärer Transport von IL-6-Typ Zytokin-Rezeptoren (Project Head Graeve, Lutz )
• A4 - Aufklärung der Aktivierungsmechanismen des latenten transforming growth factor (TGF)-ß in der Leber zur Entwicklung likaler, inhibitorischer Strategien (Project Heads Breitkopf-Heinlein, Katja ;  Gressner, Axel )
• A5 - Regulation der Zytokinwirkung durch Plasma-Bindeproteine (Project Head Jahnen-Dechent, Wilhelm )
• A06 - Retinsäure-vermittlete Regulation von Zytokinen und ihren Rezeptoren während der Nervenregeneration (Project Head Mey, Jörg )
• A07 - CXCR and CD74 receptor mechanisms of the cytokine MIF and their role in nephrotoxic nephritis (Project Heads Bernhagen, Jürgen ;  Ostendorf, Tammo ;  Weber, Christian )
• A09 - The cross-talk of BMP-7 and TGF-ß: Is BMP-7 the natural antagonist of TGF-ß in inflammatory liver diseases? (Project Heads Meurer, Steffen Klaus ;  Weiskirchen, Ralf )
• A10 - Mechanismus der P2X7-Rezeptor-vermittelten Zytokinfreisetzung (Project Head Schmalzing, Günther )
• A11 - Effects of Y-box protein-1 on the signal transduction of receptor Notch-3 and cell differentiation (Project Head Mertens, Peter Rene )
• A12 - Shedding of proinflammatory mediators by the metalloproteinases ADAM10 and ADAM17 during inflammatory leukocyte recruitment (Project Heads Ludwig, Andreas ;  Weber, Christian )
• B1 - Struktur-/Funktionsanalysen der Janus-Kinasen und deren Bedeutung für die Signaltransduktion von Zytokinen der IL-6-Familie (Project Head Heinrich, Peter C. )
• B02 - IL-6-vermittelte, STAT-independent signalling pathways (Project Head Schaper, Fred )
• B03 - Signaltransduktion der Leptinrezeptors im Vergleich zur gp130-vermittelten Signaltransduktion (Project Head Becker, Walter )
• B04 - Cross talk of NF-kB, glucocorticoids and STAT3 in the acute phase response (Project Heads Bode, Johannes Georg ;  Schaper, Fred )
• B5 - Signaltransduktion von Chemokinen in neutrophilen Granulozyten: Molekulare Mechanismen, Regulation und Relevanz von Calcium-Influx (Project Head Lückhoff, Andreas )
• B06 - Molekulare Mechanismen der Oncostatin M-vermittelten Signaltransduktion und deren Bedeutung in der Entzündung (Project Head Hermanns, Heike M. )
• B7 - Signaltransduktion der Interleukin-6-Typ Zytokin-vermittelten Migration von T-Zellen (Project Heads Heinrich, Peter C. ;  Schaper, Fred )
• B08 - Cytokine-dependent regulation of the MAD1 promoter and the MAD1 protein (Project Head Lüscher, Bernhard )
• B10 - The TGF-ß1/Id2/IRF8 signalling pathway in development of antigen presenting dendritic cells (Project Head Zenke, Martin )
• B11 - Untersuchungen zur Signaltransduktion von Interleukin-27 und dessen Wirkung auf Immunzellen (Project Head Haan, Serge )
• B12 - Dynamics and topology of the Jak/STAT signalling pathway (Project Head Müller-Newen, Gerhard )
• C01 - Transkriptionelle Regulation hepatobiliärer organischer Anionentransporter durch proinflammatorische Zytokine (Project Head Geier, Andreas )
• C03 - Die TIMP-1/MMP-9-Interaktion: Struktur- /Funktionsanalysen in vitro und am Tiermodell akuter und chronisch fibrosierender Erkrankungen (Project Head Roeb, Elke )
• C04 - Effects of transkription factor YB-1 on the proinflammatory mesangial cell phenotype (Project Head Mertens, Peter Rene )
• C5 - Einfluß von Myokarditis und inflammatorischen Zytokinen auf den kardiomyozytären Glucosestoffwechsel (Project Head Fischer, Yvan )
• C6 - Charakterisierung autoreaktiver T-Zellantworten auf das bullöse Pemphigoid-Antigen 2 (BPAG2) bei Patienten mit bullösem Pemphigoid und gesunden Trägern des HLA-DQß1*0301-Allels (Project Heads Hertl, Michael ;  Merk, Hans F. )
• C07 - Interventions in the PDGF system: A new therapy approach in inflammatory renal disease (Project Heads Floege, Jürgen ;  Ostendorf, Tammo )
• C8 - Expression von Smad7 zur Antagonisierung profibrogener Effekte von TGF-ß während der Transdifferenzierung von hepatischen Sternzellen (Project Head Dooley, Ph.D., Steven )
• C11 - Regulation of IL-31 in pathogenesis and therapy of T-cell mediated allergic immediate type reactions and inflammatory skin diseases (Project Heads Baron, Jens Malte ;  Lüscher, Bernhard )
• C12 - Regulatory role of YB-1 for the functional expression of the chemokine RANTES in inflammatory processes (Project Heads Mertens, Peter Rene ;  Weber, Christian )
• C14 - Role of gp130-dependent signalling in hepatocytes for the regulation of immune responses in local and systemic models of inflammation (Project Head Trautwein, Christian )
• C15 - The Role of TNF and Fas-mediated signalling in models of inflammatory liver injury (Project Heads Liedtke, Christian ;  Trautwein, Christian )
• C16 - The EGF-receptor-ligand amphiregulin and ventilator-induced inflammation (biotrauma) (Project Heads Uhlig, Stefan ;  Uhlig, Ulrike )
• Z01 - Konfokale Laser-scanning Mikroskopie (Project Head Müller-Newen, Gerhard )
• Z02 - Central Services of the Collaborative Research Program (Project Heads Floege, Jürgen ;  Müller-Newen, Gerhard )
• Z03 - Proteinanalytik/Proteomics (Project Heads Fischer, Rainer ;  Hoffmann, Kurt ;  Knüchel-Clarke, Ruth ;  Krieg, Rene )

• Applicant Institution: Rheinisch-Westfälische Technische Hochschule Aachen
• Participating University: Heinrich-Heine-Universität Düsseldorf
• Spokesperson: Professor Dr. Jürgen Floege