title: Generation of Soluble Interleukin-11 and Interleukin-6 Receptors: A Crucial Function for Proteases during Inflammation.
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.
authors: Institute of Biochemistry, Kiel University, 24118 Kiel, Germany.
authors: Juliane
authors: J
authors: Lokau
authors: Institute of Biochemistry, Kiel University, 24118 Kiel, Germany.
authors: Maria
authors: M
authors: Agthe
authors: Institute of Biochemistry, Kiel University, 24118 Kiel, Germany.
authors: Christoph
authors: 0000-0003-4939-6950
authors: C
authors: Garbers
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D017370:Interleukin-11 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D053702:Receptors, Interleukin-11 / Q000235:genetics / Q000378:metabolism*; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D017370:Interleukin-11; D015850:Interleukin-6; D053702:Receptors, Interleukin-11; D019947:Receptors, Interleukin-6