Abstract
The pleiotropic physiological functions of interleukin (IL-)6 type cytokines range from embryonic development and tissue homoeostasis to neuronal development and T cell differentiation. In contrast, imbalance of the well-controlled cytokine signaling network leads to chronic inflammatory diseases and cancer. IL-6 and IL-11 both signal through a homodimer of the ubiquitously expressed β-receptor glycoprotein 130 (gp130). Specificity is gained through an individual IL-6/IL-11 α-receptor, which does not directly participate in signal transduction, although the initial cytokine binding event to the α-receptor leads to the final complex formation with the β-receptors. Both cytokines activate the same downstream signaling pathways, which are predominantly the mitogen-activated protein kinase (MAPK)-cascade and the Janus kinase/signal transducer and activator of transcription (Jak/STAT) pathway. However, recent studies have highlighted divergent roles of the two related cytokines. Here, we will discuss how the biochemical similarities are translated into unique and non-redundant functions of IL-6 and IL-11 in vivo and illustrate strategies for cytokine-specific therapeutic intervention.
About the authors
Christoph Garbers received his diploma degree in Pharmacy in 2007 at the University of Kiel, Germany, and his licensure as pharmacist in 2008. He joined the group ‘Cytokine and Metalloproteinase Research’ at the Institute of Biochemistry of the University of Kiel in 2008 and obtained his Dr. rer. nat. in 2011 for the functional characterization of ADAM proteases in IL-6R shedding. He then moved to the Heinrich-Heine-University Düsseldorf, Germany, and has worked since 2011 at the Institute of Biochemistry and Molecular Biology II as a postdoctoral research associate. His current interests are focused on limited proteolysis of cytokine receptors and signal transduction of IL-6 type cytokines.
Jürgen Scheller finished his diploma study of Biology in 1997 at the Georg-August University of Göttingen, Germany and obtained his Dr. rer. nat. in 1999 for the role of MPH1 in DNA-repair of Saccharomyces cerevisiae. He joined the group ‘Phytoantibodies’ at the Leibniz-Institut IPK in Gatersleben, Germany in 1999. From 1999 to 2002 he worked on spider silk proteins from transgenic plants. In 2002 he became assistant professor at the Biochemical Institute at Christian-Albrechts-Universität of Kiel, Germany. In 2008 he became W2-Professor for ‘Cytokine Signaling’ within the Cluster of Excellence ‘Inflammation at Interfaces’ at Christian-Albrechts-Universität of Kiel, Germany. In 2010 he moved to the Heinrich-Heine-University and became the director of the Institute of Biochemistry and Molecular Biology II as a W3-Professor. His present interests are focused on in vitro and in vivo studies of IL-6-type cytokines.
This work was funded by grants from the Deutsche Forschungsgemeinschaft, Bonn, Germany (to J.S. – DFG SCHE 907/2) and the Research Commission of the Medical Faculty of the Heinrich-Heine-University (to C.G. and J.S.).
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