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Dissecting Interleukin-6 Classic- and Trans-Signaling in Inflammation and Cancer

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Inflammation and Cancer

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1725))

Abstract

Interleukin-6 is a cytokine synthesized by many cells in the human body. IL-6 binds to a membrane bound IL-6R, which is only present on hepatocytes, some epithelial cells and some leukocytes. The complex of IL-6 and IL-6R binds to the ubiquitously expressed receptor subunit gp130, which forms a homodimer and thereby initiates intracellular signaling via the JAK/STAT and the MAPK pathways. IL-6R expressing cells can cleave the receptor protein to generate a soluble IL-6R (sIL-6R), which can still bind IL-6 and can associate with gp130 and induce signaling even on cells, which do not express IL-6R. This paradigm has been called IL-6 trans-signaling whereas signaling via the membrane bound IL-6R is referred to as classic signaling. We have generated several molecular tools to differentiate between IL-6 classic- and trans-signaling and to analyze the consequence of cellular IL-6 signaling in vivo.

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Acknowledgments

This work was supported by the Deutsche Forschungsgemeinschaft (DFG), Bonn, Germany (SFB654, project C5; SFB841, project C1; SFB877, project A1, A10), by the Bundesministerium für Bildung und Forschung www.bmbf.de (grant number InTraSig, project B) and by the German Cluster of Excellence ‘Inflammation at Interfaces’.

Competing Interests

S.R.-J. has acted as a consultant and speaker to Chugai, Genentech Roche, AbbVie, Sanofi and Pfizer. He is the inventor of the sgp130Fc protein and he is listed as an inventor on patents owned by CONARIS Research Institute, which develops the sgp130Fc protein (Olamkicept) together with Ferring Pharmaceuticals, and he has stock ownership in CONARIS. C.G. has nothing to disclose.

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  1. Institute of Biochemistry, Kiel University, Kiel, Germany

    Christoph Garbers & Stefan Rose-John

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  1. Christoph Garbers
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  2. Stefan Rose-John
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Correspondence to Stefan Rose-John .

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Editors and Affiliations

  1. Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia

    Brendan J. Jenkins

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Garbers, C., Rose-John, S. (2018). Dissecting Interleukin-6 Classic- and Trans-Signaling in Inflammation and Cancer. In: Jenkins, B. (eds) Inflammation and Cancer. Methods in Molecular Biology, vol 1725. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7568-6_11

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  • DOI: https://doi.org/10.1007/978-1-4939-7568-6_11

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  • Publisher Name: Humana Press, New York, NY

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