Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor transsignaling responses

Eur J Biochem. 2001 Jan;268(1):160-7. doi: 10.1046/j.1432-1327.2001.01867.x.


Signal transduction in response to interleukin-6 (IL-6) requires binding of the cytokine to its receptor (IL-6R) and subsequent homodimerization of the signal transducer gp130. The complex of IL-6 and soluble IL-6R (sIL-6R) triggers dimerization of gp130 and induces responses on cells that do not express membrane bound IL-6R. Naturally occurring soluble gp130 (sgp130) can be found in a ternary complex with IL-6 and sIL-6R. We created recombinant sgp130 proteins that showed binding to IL-6 in complex with sIL-6R and inhibited IL-6/sIL-6R induced proliferation of BAF/3 cells expressing gp130. Surprisingly, sgp130 proteins did not affect IL-6 stimulated proliferation of BAF/3 cells expressing gp130 and membrane bound IL-6R, indicating that sgp130 did not interfere with IL-6 bound to IL-6R on the cell surface. Additionally, sgp130 partially inhibited proliferation induced by leukemia inhibitory factor (LIF) and oncostatin M (OSM) albeit at higher concentrations. Recombinant sgp130 protein could be used to block the anti-apoptotic effect of sIL-6R on lamina propria cells from Crohn disease patients. We conclude that sgp130 is the natural inhibitor of IL-6 responses dependent on sIL-6R. Furthermore, recombinant sgp130 is expected to be a valuable therapeutic tool to specifically block disease states in which sIL-6R transsignaling responses exist, e.g. in morbus Crohn disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Reaction
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / isolation & purification
  • Antigens, CD / metabolism
  • Antigens, CD / pharmacology*
  • Apoptosis
  • Cell Division / drug effects
  • Cells, Cultured
  • Crohn Disease / pathology
  • Cytokine Receptor gp130
  • Humans
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / isolation & purification
  • Membrane Glycoproteins / metabolism
  • Membrane Glycoproteins / pharmacology*
  • Mice
  • Protein Synthesis Inhibitors / pharmacology
  • Receptors, Interleukin-6 / antagonists & inhibitors*
  • Receptors, Interleukin-6 / metabolism
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Signal Transduction
  • Solubility
  • Transfection
  • Tumor Cells, Cultured


  • Antigens, CD
  • IL6ST protein, human
  • Il6st protein, mouse
  • Membrane Glycoproteins
  • Protein Synthesis Inhibitors
  • Receptors, Interleukin-6
  • Recombinant Proteins
  • Cytokine Receptor gp130