• Media type: E-Article
  • Title: Soluble gp130 is the natural inhibitor of soluble interleukin‐6 receptor transsignaling responses
  • Contributor: Jostock, Thomas; Müllberg, Jürgen; Özbek, Suat; Atreya, Raja; Blinn, Guido; Voltz, Nicole; Fischer, Martina; Neurath, Markus F.; Rose‐John, Stefan
  • imprint: Wiley, 2001
  • Published in: European Journal of Biochemistry
  • Language: English
  • DOI: 10.1046/j.1432-1327.2001.01867.x
  • ISSN: 0014-2956; 1432-1033
  • Keywords: Biochemistry
  • Origination:
  • Footnote:
  • Description: <jats:p>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.</jats:p>
  • Access State: Open Access