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. 1992 Apr;83(4):373–378. doi: 10.1111/j.1349-7006.1992.tb00117.x

Soluble Interleukin‐6 Receptor Is Released from Receptor‐bearing Cell Lines in vitro

Toshiharu Nakajima 1,†, Shinji Yamamoto 1, Ming Cheng 1, Kiyoshi Yasukawa 2, Toshio Hirano 3, Tadamitsu Kishimoto 4, Tohru Tokunaga 1, Mitsuo Honda 1,✉
PMCID: PMC5918830  PMID: 1506271

Abstract

Soluble interleukin‐6 receptor (sIL‐6R) was found to be spontaneously released from human myeloma cell line U266 cells into culture supernatant, and was quantitatively measured with a fluorescence sandwich enzyme‐linked immunosorbent assay employing antibodies specific to IL‐6R. The supernatant IL‐6R was generated only from IL‐6R‐positive cell lines; myeloma cell lines RPMI8226 and RPMI1788, and myelomonocytic cell lines U937, THP‐1, and HL‐60. In contrast, it was not released from the IL‐6R‐negative cells; T cell line MoIt‐4 and Burkitt lympboma cell line Raji. SDS‐PAGE analysis of the soluble IL‐6R from U266 cells suggested a molecular weight of approximately 50‐55 kDa, 25–30 kDa smaller than the mature cell surface receptor. These results suggest that the generation of soluble IL‐6R may be a maker of myeloma cells and myelomonocytic cells.

Keywords: Key words, Human IL‐6 receptor, Soluble interleukin receptor, Recombinant soluble IL‐6 receptor, Interleukin‐6

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REFERENCES

  • 1. ) Hirano , T. and Kishimoto , T.Interleukin‐6 (IL‐6) . Handb. Exp. Pharmacol , 86 , 633 – 665 ( 1991. ). [Google Scholar]
  • 2. ) Zilberstein , A. , Ruggieri , R. , Korn , J. H. and Revel , M.Structure and expression of cDNA and genes for human interferon‐beta‐2, a distinct species by growth stimulatory cytokines . EMBO. J. , 5 , 2529 – 2537 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. ) May , L. T. , Helfgott , D. C. and Sehgal , P. B.Anti‐β‐interferon antibodies inhibit the increased expression of HLA‐B7 mRNA in tumor necrosis factor treated human fibroblasts: structural studies of the/32 interferon involved . Proc. Natl. Acad. Set. USA , 83 , 8957 – 8961 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. ) van Damme , J. , Opdenakker , G. , Simpson , R. G. , Rubira , M. R. , Cayphas , S. , Vink , A. , Billiau , A. and Scick , J. V.Identification of the human 26‐kDa protein, interferon β2 (IFN‐β2), as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor . J. Exp. Med. , 165 , 914 – 919 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. ) Garman , R. D. , Jacobs , K. A. , Clark , S. C. and Raulet , D. H.B‐cell‐stimulatory factor (β2 interferon) functions as a second signal for interleukin 2 production by mature murine T cells . Proc. Natl. Acad. Sci. USA , 84 , 7629 – 7633 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. ) Lotz , M. , Jirik , F. , Kabouridis , R. , Tsoukas , T. , Hirano , T. , Kishimoto , T. and Carson , D. A.BSF‐2/IL‐6 is a costimulant for human thymocytes and T lymphocytes . J. Exp. Med. , 167 , 1253 – 1258 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. ) Takai , Y. , Wong , G. G. , Clark , S. C , Burakoff , S. J. and Herrman , S. H.B cell stimulatory factor‐2 is involved in the differentiation of cytotoxic T lymphocytes . J. Immunol. , 140 , 508 – 512 ( 1988. ). [PubMed] [Google Scholar]
  • 8. ) Gauldie , J. , Richard , C , Harnish , D. , Lansdorp , P. and Baumann , H.Interferon /β2/B‐cell stimulatory factor type 2 shares identity with monocyte derived hepatocyte‐stimulating factor and regulates the major acute phase protein response in liver cells . Proc. Natl. Acad. Sci. USA , 86 , 7251 – 7255 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. ) Andus , T. , Geiger , T. , Hirano , T. , Northoff , H. , Ganter , U. , Bauer , J. , Kishimoto , T. and Heinrich , P. C.Recombinant human B cell stimulatory factor 2 (BSF‐2/ INF‐/β2) regulates β‐fibrinogen and albumin mRNA levels in Fao‐9 cells . FEBS Lett. , 221 , 18 – 22 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Satoh , T. , Nakamura , S. , Taga , T. , Matsuda , T. , Hirano , T. , Kishimoto , T. and Kaziro , Y.Induction of neural differentiation in PC 12 cells by B cell stimulatory factor/ interleukin 6 . Mol. Cell. Biol. , 8 , 3546 – 3549 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. ) Ikebuchi , K. , Wong , G. G. , Clark , S. C , Ihle , J. N. , Hirai , Y. and Ogawa , M.Interleukin‐6 enhancement of inter‐leukin‐3‐dependent proliferation of multipotential hemopoietic progenitors . Proc. Natl. Acad. Sci. USA , 84 , 9035 – 9039 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. ) Taga , T. , Kawanishi , Y. , Hardy , R. R. , Hirano , T. , and Kishimoto , T.Receptors for B cell stimulatory factor 2. Quantitation, specificity, distribution, and regulation of expression . J. Exp. Med. , 166 , 967 – 981 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. ) Yamasaki , K. , Taga , T. , Hirata , Y. , Yawata , H. , Kawanishi , Y. , Seed , B. , Taniguchi , T. , Hirano , T. and Kishimoto , T.Cloning and expression of the human interleukin‐6 (BSF‐2/IFN‐/β2) receptor . Science , 241 , 825 – 828 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Hirata , Y. , Taga , T. , Hibi , M. , Nakano , N. , Hirano , T. and Kishimoto , T.Characterization of IL‐6 receptor expression by monoclonal and polyclonal antibodies . Immunol. , 143 , 2900 – 2906 ( 1989. ). [PubMed] [Google Scholar]
  • 15. ) Taga , T. , Hibi , M. , Hirata , Y. , Yasukawa , K. , Masuda , T. , Hirano , T. and Kishimoto , T.Interleukin‐6 triggers the association of its receptor with a possible signal transducer, gp130 . Cell , 58 , 573 – 581 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Novick , D. , Engelmann , H. , Wallach , D. and Rubinstein , M.Soluble cytokine receptors are present in normal human urine . J. Exp. Med. , 170 , 1409 – 1414 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. ) Novick , D. , Engelmann , H. and Wallach , D.Purification of soluble cytokine receptors from normal human urine by ligand‐affinity and immunoaffinity chromatography . J. Chromatogr. , 510 , 331 – 337 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Yasukawa , K. , Hirano , T. , Watanabe , Y. , Muratani , K. , Matsuda , T. , Nakai , S. and Kishimoto , T.Structure and expression of human B cell stimulatory factor‐2 (BSF‐2/ IL‐6) gene . EMBO J. , 6 , 2939 – 2945 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. ) Yasukawa , K. , Saito , T. , Fukunaga , T. , Sekimori , Y. , Koishihara , Y. , Fukui , H. , Osugi , Y. , Matsuda , T. , Yawata , H. , Hirano , T. , Taga , T. and Kishimoto , T.Purification and characterization of soluble human IL‐6 receptor expressed in CHO cell . J. Biochem. , 108 , 673 – 679 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Honda , M. , Kitamura , K. , Matsuda , K. , Yokota , Y. , Yamamoto , N. , Mitsuyasu , R. , Chermann , J.‐C. and Tokunaga , T.Soluble IL‐2 receptor in AIDS: correlation of its serum level with the classification of HIV‐induced diseases and its characterization . Immunol. , 142 , 4248 – 4255 ( 1989. ). [PubMed] [Google Scholar]
  • 21. ) Honda , M. , Nagao , S. , Yamamoto , N. , Tanaka , Y. , Tozawa , H. and Tokunaga , T.Fluorescence sandwich enzyme‐linked immunosorbent assay for detecting human interleukin‐2 receptors . J. Immunol. Methods , 110 , 129 – 136 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Laemmli , U. K.Cleavage of structural proteins during the assembly of the head of bacteriophage T4 . Nature , 227 , 680 – 685 ( 1970. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Saito , T. , Yasukawa , K. , Suzuki , H. , Futatsugi , K. , Fukunaga , T. , Yokomizo , C , Koishihara , Y. , Fukui , H. , Ohsugi , Y. , Yawata , H. , Hirano , T. , Taga , T. and Kishimoto , T.Preparation of soluble murine IL‐6 receptor and anti‐murine IL‐6 receptor antibodies . J. Immunol , 147 , 168 – 173 ( 1991. ). [PubMed] [Google Scholar]
  • 24. ) Gavin , J. R. , Buell , D. N. and Roth , J.Water soluble insulin receptors from lymphocytes . Science , 178 , 168 – 189 ( 1972. ). [DOI] [PubMed] [Google Scholar]
  • 25. ) Weber , W. , Gill , G. and Spiess , J.Production of an epidermal growth factor receptor‐related protein . Science , 224 , 294 – 297 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 26. ) Rubin , L. A. , Kurman , C. C , Fritz , M. E. , Biddison , W. E. , Boutin , B. , Yachoan , R. and Nelson , D. L.Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro . J. Immunol , 135 , 3172 – 3177 ( 1985. ). [PubMed] [Google Scholar]
  • 27. ) Engelmann , H. , Aderka , D. , Rubinstein , M , Rotman , D. and Wallach , D.A tumor necrosis factor‐binding protein purified to homogeneity from human urine protects cells from tumor necrosis factor toxicity . J. Biol. Chem. , 264 , 11974 – 11980 ( 1989. ). [PubMed] [Google Scholar]
  • 28. ) Olsson , I. , Lantz , M , Nilsson , E. , Peetre , C , Thysell , H. , Groubb , A. and Adolf , G.Isolation and characterization of a tumor necrosis factor binding protein from urine . Eur. J. Haematol , 42 , 270 – 278 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 29. ) Srckinger , P. , Isaaz , S. and Dayer , J.‐M.Purification and biologic characterization of a specific tumor necrosis factor alpha inhibitor . Biol. Chem. , 264 , 11966 – 11973 ( 1989. ). [PubMed] [Google Scholar]
  • 30. ) Nakajima , T. , Sarfati , M. and Delespesse , G.Relationship between human IgE‐binding factor (IgE‐BF) and lymphocyte receptors for IgE . J. Immunol , 139 , 848 – 854 ( 1987. ). [PubMed] [Google Scholar]
  • 31. ) Sarfati , M. , Bron , D. , Lagneaux , L. , Fonteyn , C , Frost , H. and Delespesse , G.Elevation of IgE‐binding factors in serum of patients with B cell‐derived chronic lymphocytic leukemia . Blood , 71 , 94 – 98 ( 1988. ). [PubMed] [Google Scholar]
  • 32. ) Cosma , D. , Khoury , G. and Jay , G.Three classes of mouse H‐2 messenger RNA distinguished by analysis of cDNA clones . Nature , 295 , 73 – 76 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 33. ) Maloy , W. L. , Coligan , J. E. , Barra , Y. , and Jay , G.Detection of a secreted form of the murine H‐2 class I antigen with an antibody against its predicted carboxyl terminus . Proc. Natl Acad. Sci. USA , 81 , 1216 – 1220 ( 1984. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34. ) Sachs , D. H. , Kiszkiss , P. and Kim , K. J.Release of la antigens by a cultured B cell line . J. Immunol , 124 , 2130 – 2136 ( 1980. ). [PubMed] [Google Scholar]
  • 35. ) Fujimoto , J. , Levy , S. and Levy , R.Spontaneous release of Leu‐2 (T8) molecule from human T cells . J. Exp. Med. , 158 , 752 – 766 ( 1983. ). [DOI] [PMC free article] [PubMed] [Google Scholar]

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