The balance of interleukin (IL)-6, IL-6soluble IL-6 receptor (sIL-6R), and IL-6sIL-6Rsgp130 complexes allows simultaneous classic and trans-signaling

Journal of Biological Chemistry

Volumn 293, Issue 18, 2018, Pages 6762-6775

  Baran, Paul ^a   Hansen, Selina ^a   Waetzig, Georg H ^b   Akbarzadeh, Mohammad ^a   Lamertz, Larissa ^a   Huber, Heinrich J ^c   Reza Ahmadian, M ^a   Moll, Jens M ^a   Scheller, Jürgen ^a  

^a HEINRICH HEINE UNIVERSITY   (Germany)

^b CONARIS Research Institute AG ^*  (Germany)

^c OTTO VON GUERICKE UNIVERSITY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

SIGNALING;

BUFFER SYSTEM; CONCENTRATION RANGES; HUMAN SERUM; IL-6 EXPRESSION; MEMBRANE-BOUND; RELATIVE RATIOS; SERUM LEVELS; SINGLE-DOMAIN ANTIBODIES;

IMMUNOLOGY;

GLYCOPROTEIN GP 130; INTERLEUKIN 6; INTERLEUKIN RECEPTOR; NANOBODY; SOLUBLE GLYCOPROTEIN GP 130; SOLUBLE INTERLEUKIN 6 RECEPTOR; UNCLASSIFIED DRUG; VHH6 ANTIBODY; EPITOPE; IL6 PROTEIN, HUMAN; INTERLEUKIN 6 RECEPTOR; RECOMBINANT PROTEIN;

ARTICLE; BLOOD; CONCENTRATION (PARAMETERS); ENZYME LINKED IMMUNOSORBENT ASSAY; HUMAN; IMMUNOPRECIPITATION; INFLAMMATION; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; CELL LINE; IMMUNOLOGY; METABOLISM;

CELL LINE; CYTOKINE RECEPTOR GP130; ENZYME-LINKED IMMUNOSORBENT ASSAY; EPITOPES; HUMANS; INTERLEUKIN-6; RECEPTORS, INTERLEUKIN-6; RECOMBINANT PROTEINS; SIGNAL TRANSDUCTION; SINGLE-DOMAIN ANTIBODIES;

EID: 85046673121     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.RA117.001163     Document Type: Article

References (32)

1. Scheller, J., Chalaris, A., Schmidt-Arras, D., and Rose-John, S. (2011) The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim. Biophys. Acta 1813, 878 – 888 CrossRef
2. Garbers, C., Hermanns, H. M., Schaper, F., Müller-Newen, G., Grötzinger, J., Rose-John, S., and Scheller, J. (2012) Plasticity and cross-talk of Interleukin 6-type cytokines. Cytokine Growth Factor Rev. 23, 85–97 CrossRef Medline
3. Jostock, T., Mullberg, J., Ozbek, S., Atreya, R., Blinn, G., Voltz, N., Fischer, M., Neurath, M. F., and Rose-John, S. (2001) Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor transsignaling responses. Eur. J. Biochem. 268, 160 –167 CrossRef Medline
4. Horiuchi, S., Koyanagi, Y., Zhou, Y., Miyamoto, H., Tanaka, Y., Waki, M., Matsumoto, A., Yamamoto, M., and Yamamoto, N. (1994) Soluble interleukin-6 receptors released from T cell or granulocyte/macrophage cell lines and human peripheral blood mononuclear cells are generated through an alternative splicing mechanism. Eur. J. Immunol. 24, 1945–1948 CrossRef Medline
5. Matthews, V., Schuster, B., Schütze, S., Bussmeyer, I., Ludwig, A., Hund-hausen, C., Sadowski, T., Saftig, P., Hartmann, D., Kallen, K.-J., and Rose-John, S. (2003) Cellular cholesterol depletion triggers shedding of the human interleukin-6 receptor by ADAM10 and ADAM17 (TACE). J. Biol. Chem. 278, 38829 –38839 CrossRef Medline
6. Müllberg, J., Schooltink, H., Stoyan, T., Günther, M., Graeve, L., Buse, G., Mackiewicz, A., Heinrich, P. C., and Rose-John, S. (1993) The soluble interleukin-6 receptor is generated by shedding. Eur. J. Immunol. 23, 473– 480 CrossRef Medline
7. Rose-John, S. (2017) The soluble Interleukin 6 receptor: Advanced therapeutic options in inflammation. Clin. Pharmacol. Ther. 102, 591–598 CrossRef Medline
8. Garbers, C., Thaiss, W., Jones, G. W., Waetzig, G. H., Lorenzen, I., Guilhot, F., Lissilaa, R., Ferlin, W. G., Grötzinger, J., Jones, S. A., Rose-John, S., and Scheller, J. (2011) Inhibition of classic signaling is a novel function of soluble GP130 which is controlled by the ratio of interleukin 6 and soluble interleukin 6 receptor. J. Biol. Chem. 286, 42959 – 42970 CrossRef Medline
9. Akira, S., Taga, T., and Kishimoto, T. (1993) Interleukin-6 in biology and medicine. Adv. Immunol. 54, 1–78 CrossRef Medline
10. Kishimoto, T., Akira, S., Narazaki, M., and Taga, T. (1995) Interleukin-6 family of cytokines and gp130. Blood 86, 1243–1254 Medline
11. Jones, S. A. (2005) Directing transition from innate to acquired immunity: defining a role for IL-6. J. Immunol. 175, 3464 –3468
12. Gaillard, J., Pugnière, M., Tresca, J., Mani, J., Klein, B., and Brochier, J. (1999) Interleukin-6 receptor signaling: II. bio-availability of interleukin-6 in serum. Eur. Cytokine Netw. 10, 337–344 Medline
13. Mitsuyama, K., Toyonaga, A., Sasaki, E., Ishida, O., Ikeda, H., Tsuruta, O., Harada, K., Tateishi, H., Nishiyama, T., and Tanikawa, K. (1995) Soluble interleukin-6 receptors in inflammatory bowel disease: relation to circulating interleukin-6. Gut 36, 45– 49 CrossRef Medline
14. Montero-Julian, F. A. (2001) The soluble IL-6 receptors: serum levels and biological function. Cell. Mol. Biol. 47, 583–597 Medline
15. Adams, R., Burnley, R., Valenzano, C., Qureshi, O., Doyle, C., Lumb, S., Del Carmen Lopez, M., Griffin, R., McMillan, D., Taylor, R., Meier, C., Mori, P., Griffin, L., Wernery, U., et al. (2017) Discovery of a junctional epitope antibody that stabilizes IL-6 and gp80 protein:protein interaction and modulates its downstream signaling. Sci. Rep. 7, 37716 CrossRef Medline
16. Zohlnhöfer, D., Graeve, L., Rose-John, S., Schooltink, H., Dittrich, E., and Heinrich, P. (1992) The hepatic interleukin-6 receptor: down-regulation of the interleukin-6 binding subunit (gp80) by its ligand. FEBS Lett. 306, 219 –222 CrossRef Medline
17. Hibi, M., Murakami, M., Saito, M., Hirano, T., Taga, T., and Kishimoto, T. (1990) Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell 63, 1149 –1157 CrossRef Medline
18. Fischer, M., Goldschmitt, J., Peschel, C., Kallen, K. J., Brakenhoff, J. P. J., Wollmer, A., Groetzinger, J., and Rose-John, S. (1997) A designer cytokine with high activity on human hematopoietic progenitor cells. Nature Bio-tech. 15, 142–145 CrossRef
19. Crabé, S., Guay-Giroux, A., Tormo, A. J., Duluc, D., Lissilaa, R., Guilhot, F., Mavoungou-Bigouagou, U., Lefouili, F., Cognet, I., Ferlin, W., Elson, G., Jeannin, P., and Gauchat, J. F. (2009) The IL-27 p28 subunit binds cytokine-like factor 1 to form a cytokine regulating NK and T cell activities requiring IL-6R for signaling. J. Immunol. 183, 7692–7702 CrossRef Medline
20. Kallen, K. J., Grötzinger, J., Lelièvre, E., Vollmer, P., Aasland, D., Renné, C., Müllberg, J., Myer zum Büschenfelde, K. H., Gascan, H., and Rose-John, S. (1999) Receptor recognition sites of cytokines are organized as exchangeable modules. Transfer of the leukemia inhibitory factor receptor-binding site from ciliary neurotrophic factor to interleukin-6. J. Biol. Chem. 274, 11859 –11867 CrossRef Medline
21. Friederichs, K., Schmitz, J., Weissenbach, M., Heinrich, P. C., and Schaper, F. (2001) Interleukin-6-induced proliferation of pre-B cells mediated by receptor complexes lacking the SHP2/SOCS3 recruitment sites revisited. Eur. J. Biochem. 268, 6401– 6407 CrossRef Medline
22. Bataille, R., Jourdan, M., Zhang, X. G., and Klein, B. (1989) Serum levels of interleukin 6, a potent myeloma cell growth factor, as a reflect of disease
23. severity in plasma cell dyscrasias. J. Clin. Invest. 84, 2008 –2011 CrossRef Medline
24. Frieling, J. T., van Deuren, M., Wijdenes, J., van der Meer, J. W., Clement, C., van der Linden, C. J., and Sauerwein, R. W. (1995) Circulating interleukin-6 receptor in patients with sepsis syndrome. J. Infect. Dis. 171, 469 – 472 CrossRef Medline
25. Nechemia-Arbely, Y., Barkan, D., Pizov, G., Shriki, A., Rose-John, S., Ga-lun, E., and Axelrod, J. (2008) IL-6/IL-6R axis plays a critical role in acute kidney injury. J. Am. Soc. Nephrol. 19, 1106 –1115 CrossRef Medline
26. Nowell, M. A., Richards, P. J., Horiuchi, S., Yamamoto, N., Rose-John, S., Topley, N., Williams, A. S., and Jones, S. A. (2003) Soluble IL-6 receptor governs IL-6 activity in experimental arthritis: blockade of arthritis severity by soluble glycoprotein 130. J. Immunol. 171, 3202–3209 CrossRef Medline
27. Rabe, B., Chalaris, A., May, U., Waetzig, G. H., Seegert, D., Williams, A. S., Jones, S. A., Rose-John, S., and Scheller, J. (2008) Transgenic blockade of interleukin 6 transsignaling abrogates inflammation. Blood 111, 1021–1028 Medline
28. Scheller, J., Chalaris, A., Garbers, C., and Rose-John, S. (2011) ADAM17: a molecular switch controlling inflammatory and regenerative responses. Trends Immunol. 32, 380 –387 CrossRef Medline
29. Wolf, J., Waetzig, G., Chalaris, A., Reinheimer, T., Wege, H., Rose-John, S., and Garbers, C. (2016) Different soluble forms of the interleukin-6 family signal transducer gp130 fine-tune the blockade of interleukin-6 transsignaling. J. Biol. Chem. 291, 16186 –16196 CrossRef
30. Tenhumberg, S., Waetzig, G. H., Chalaris, A., Rabe, B., Seegert, D., Scheller, J., Rose-John, S., and Grötzinger, J. (2008) Structure guided optimization of the interleukin-6 transsignaling antagonist sgp130. J. Biol. Chem. 283, 27200 –27207 CrossRef Medline
31. Chalaris, A., Rabe, B., Paliga, K., Lange, H., Laskay, T., Fielding, C. A., Jones, S. A., Rose-John, S., and Scheller, J. (2007) Apoptosis is a natural stimulus of IL6R shedding and contributes to the pro-inflammatory trans-signaling function of neutrophils. Blood 110, 1748 –1755 CrossRef Medline
32. Mackiewicz, A., Rose-John, S., Schooltink, H., Laciak, M., Górny, A., and Heinrich, P. C. (1992) Soluble human interleukin-6-receptor modulates interleukin-6-dependent N-glycosylation of 1-protease inhibitor secreted by HepG2 cells. FEBS Lett. 306, 257–261 CrossRef Medline