Recombinant soluble interleukin-11 (IL-11) receptor alpha-chain can act as an IL-11 antagonist.

We have expressed a soluble N-glycosylated form of the murine interleukin-11 (IL-11) receptor alpha-chain (sIL-11R) and examined signaling in cells expressing the gp130 molecule. In the presence of gp130 but not the transmembrane IL-11R, the sIL-11R mediated IL-11-dependent differentiation of M1 leukemic cells and proliferation in Ba/F3 cells. Early intracellular events stimulated by the sIL-11R including phosphorylation of gp130, STAT 3, and SHP-2 were similar to signaling through the transmembrane IL-11R. IL-11 bound to sIL-11R with low affinity (kd 10 to 50 nmol/L). Binding of sIL-11R to gp130 was IL-11 dependent with intermediate affinity (kd 1.5 to 3.0 nmol/L). However, the concentration of IL-11 required for signaling through the sIL-11R was 10- to 20-fold greater than that required for cells expressing the transmembrane IL-11R and gp130 in the absence of sIL-11R. Furthermore, the sIL-11R was capable of antagonizing the activity of IL-11 when tested on cells expressing the transmembrane IL-11R and gp130. We propose that the observed IL-11 antagonism by the sIL-11R may depend on limiting numbers of gp130 molecules on cells already expressing the transmembrane IL-11R.

[1]  J. Heath,et al.  Mediation of interleukin-11-dependent biological responses by a soluble form of the interleukin-11 receptor. , 1996, The Biochemical journal.

[2]  D. Golde,et al.  Soluble cytokine receptors. , 1996, Blood.

[3]  N. Udagawa,et al.  Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[4]  G. Yancopoulos,et al.  The alphas, betas, and kinases of cytokine receptor complexes , 1993, Cell.

[5]  F. Finkelman,et al.  Recombinant soluble murine IL-4 receptor can inhibit or enhance IgE responses in vivo. , 1993, Journal of immunology.

[6]  G. Yancopoulos,et al.  The molecular biology of the CNTF receptor , 1993, Current Opinion in Neurobiology.

[7]  S. Burstein,et al.  Leukemia inhibitory factor and interleukin‐11 promote maturation of murine and human megakaryocytes in vitro , 1992, Journal of cellular physiology.

[8]  S. Akira,et al.  Interleukin-6 and its receptor: a paradigm for cytokines. , 1992, Science.

[9]  David J. Anderson,et al.  CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp130 , 1992, Cell.

[10]  D. Hilton,et al.  Kinetic analyses of the binding of leukemia inhibitory factor to receptor on cells and membranes and in detergent solution. , 1992, The Journal of biological chemistry.

[11]  D. Hilton.  LIF: lots of interesting functions. , 1992, Trends in biochemical sciences.

[12]  C. Thut,et al.  Leukemia inhibitory factor receptor is structurally related to the IL‐6 signal transducer, gp130. , 1991, The EMBO journal.

[13]  David A. Williams,et al.  Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[14]  T. Hirano,et al.  Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130 , 1989, Cell.