sIL-6R: more than an agonist?
On target cells, interleukin-6 (IL-6) interacts with its receptor complex consisting of the membrane-bound IL-6 receptor (IL-6R) and the signal transducing protein gp130. IL-6R can exist as a soluble protein (sIL-6R), which binds the ligand IL-6. This soluble complex can bind to gp130 on cells that lack the membrane-bound IL-6R and initiate signaling. This process is named transsignaling. The significance of transsignaling via sIL-6R is underlined by different publications and exceeds very probably the significance of the membrane-bound IL-6R. It is the general assumption that sIL-6R acts as an agonist in combination with IL-6 resulting in an enhancement of the IL-6 effects. In this article, we suppose 'non-agonistic' properties. There are several publications that give reasons to speculate that sIL-6R (a) has IL-6-antagonistic effects, (b) has orphan properties and (c) interacts with yet unknown binding partners different from IL-6. Knowledge about additional properties of sIL-6R will enlarge the biologic understanding of this molecule and might give an explanation for the sometimes contrasting effects of the cytokine IL-6.
Knüpfer
Heike
H
Institute of Clinical Pharmacology, University of Leipzig, Härtelstrasse 16-18, Leipzig, Germany. Heike.Knuepfer@medizin.uni-leipzig.de
Preiss
Rainer
R
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D050822:Cytokine Receptor gp130 / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D051381:Rats; D019947:Receptors, Interleukin-6 / Q000819:agonists* / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D000093242:Interleukin-6 Inhibitors
D050822:Cytokine Receptor gp130; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins; D000093242:Interleukin-6 Inhibitors; C519852:olamkicept