sIL-6R: more than an agonist?

Immunol Cell Biol. 2008 Jan;86(1):87-91. doi: 10.1038/sj.icb.7100113. Epub 2007 Aug 28.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Cytokine Receptor gp130 / immunology
  • Cytokine Receptor gp130 / metabolism
  • Humans
  • Inflammation / immunology
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism*
  • Mice
  • Protein Binding
  • Rats
  • Receptors, Interleukin-6 / agonists*
  • Receptors, Interleukin-6 / immunology
  • Receptors, Interleukin-6 / metabolism*
  • Recombinant Fusion Proteins / antagonists & inhibitors
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / immunology*

Substances

  • Interleukin-6
  • Receptors, Interleukin-6
  • Recombinant Fusion Proteins
  • Cytokine Receptor gp130
  • olamkicept