Trans-signaling of interleukin-6 (IL-6) is mediated by the soluble IL-6 receptor, but not by soluble CD5

Biochem Biophys Res Commun. 2017 Mar 18;484(4):808-812. doi: 10.1016/j.bbrc.2017.01.174. Epub 2017 Jan 31.

Abstract

IL-6 exerts its pleiotropic activities on its target cells via the IL-6 alpha-receptor (IL-6R), which is expressed on a limited number of cell types. IL-6 can further signal via soluble forms of its receptor (sIL-6R), a process that has been termed trans-signaling. Recently, CD5 was described as an alternative alpha-receptor for IL-6 on B cells leading to the phosphorylation of the transcription factor STAT3 via the signal-transducing β-receptor gp130 in a Jak2-dependent manner. In this study, we sought to investigate whether IL-6 was also able to signal via soluble CD5 (sCD5) analogous to IL-6 trans-signaling. We show that IL-6 indeed binds to sCD5, but that this does not lead to the activation of signal transduction or cell proliferation. Furthermore, sCD5 did also not interfere with IL-6 classic signaling, suggesting that the affinity between the two proteins was too weak to provoke a biological effect. Thus, trans-signaling of IL-6 can only occur via sIL-6R, but not sCD5.

Keywords: CD5; Interleukin-6; STAT3; Trans-signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • CD5 Antigens / chemistry*
  • CD5 Antigens / metabolism*
  • Hep G2 Cells
  • Humans
  • Interleukin-6 / chemistry*
  • Interleukin-6 / metabolism*
  • Protein Binding
  • Receptors, Interleukin-6 / chemistry*
  • Receptors, Interleukin-6 / metabolism*
  • Signal Transduction / physiology
  • Solubility

Substances

  • CD5 Antigens
  • Interleukin-6
  • Receptors, Interleukin-6