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Mediators of Inflammation
Volume 2016 (2016), Article ID 1785021, 10 pages
http://dx.doi.org/10.1155/2016/1785021
Review Article

Generation of Soluble Interleukin-11 and Interleukin-6 Receptors: A Crucial Function for Proteases during Inflammation

Institute of Biochemistry, Kiel University, 24118 Kiel, Germany

Received 8 May 2016; Accepted 14 June 2016

Academic Editor: Elaine Hatanaka

Copyright © 2016 Juliane Lokau et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The cytokines interleukin-11 (IL-11) and IL-6 are important proteins with well-defined pro- and anti-inflammatory functions. They activate intracellular signaling cascades through a homodimer of the ubiquitously expressed signal-transducing β-receptor glycoprotein 130 (gp130). Specificity is gained through the cell- and tissue-specific expression of the nonsignaling IL-11 and IL-6 α-receptors (IL-11R and IL-6R), which determine the responsiveness of the cell to these two cytokines. IL-6 is a rare example, where its soluble receptor (sIL-6R) has agonistic properties, so that the IL-6/sIL-6R complex is able to activate cells that are usually not responsive to IL-6 alone (trans-signaling). Recent evidence suggests that IL-11 can signal via a similar trans-signaling mechanism. In this review, we highlight similarities and differences in the functions of IL-11 and IL-6. We summarize current knowledge about the generation of the sIL-6R and sIL-11R by different proteases and discuss possible roles during inflammatory processes. Finally, we focus on the selective and/or combined inhibition of IL-6 and IL-11 signaling and how this might translate into the clinics.