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The soluble interleukin‐6 receptor is generated by shedding
Abstract
The ligand‐binding subunit (gp80) of the human interleukin‐6 receptor (IL‐6R) was transiently expressed in COS‐7 cells. The metabolically labeled protein was shown to be quantitatively released from the membrane within 20 h. We identified the protein released from the transfected COS‐7 cells after purification to homogeneity and N‐terminal sequencing as a soluble form of the gp80/IL‐6R. Shedding of the gp80 protein was strongly induced by 4β‐phorbol‐12‐myristate‐13‐acetate, indicating that the process was regulated by protein kinase C (PKC). This was further corroborated by the finding that co‐transfection of a PKC expression plasmid led to enhanced shedding of the gp80 protein. Since shedding of gp80 could not be prevented by treatment of the cells with inhibitors of all known classes of proteases, a novel protease seems to be involved. As a control, an unrelated membrane protein (vesicular stomatitis virus glycoprotein) was transfected into COS‐7 cells and analyzed for shedding. Since the turnover of this protein was not mediated by shedding, we conclude that the release of gp80 from COS‐7 cells is a specific process. The shed gp80 protein specifically binds IL‐6, and this complex shows biological activity on human hepatoma cells. Human peripheral blood monocytes released a soluble form of the gp80 protein into the culture medium upon PMA treatment indicating that PKC‐regulated shedding is the physiological mechanism of generation of the soluble IL‐6R.
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Cites
Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas
Kawano, M., Hirano, T., Matsuda, T., Taga, T., Horii, Y., Iwato, K., Asaoku, H., Tang, B., Tanabe, O., Tanaka, H., et al. (1988) · Nature · doi:10.1038/332083a0 · Cited by 1,633
Cited by
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514
The pro- and anti-inflammatory properties of the cytokine interleukin-6
Scheller, J., Chalaris, A., Schmidt-Arras, D., & Rose-John, S. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.01.034 · Cited by 3,212
Self-citationInterleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway
HEINRICH, P. C., BEHRMANN, I., MÜLLER-NEWEN, G., SCHAPER, F., & GRAEVE, L. (1998) · Biochemical Journal · doi:10.1042/bj3340297 · Cited by 2,130
Self-citationAge-Associated Increased Interleukin-6 Gene Expression, Late-Life Diseases, and Frailty
Ershler, W. B., & Keller, E. T. (2000) · Annual Review of Medicine · doi:10.1146/annurev.med.51.1.245 · Cited by 1,282
(2012) · The Lancet · doi:10.1016/s0140-6736(12)60110-x · Cited by 1,146
Rose-John, S. (2012) · International Journal of Biological Sciences · doi:10.7150/ijbs.4989 · Cited by 1,040
“Interestingly, a soluble form of the IL-6R (sIL-6R) has been found in body fluids such as urine and blood [13] and it was shown that in humans, the sIL-6R could be generated by two different mechanisms, limited proteolysis of the membrane bound receptor by the metalloprotease ADAM17 [14] and by translation of a differ…”
BackgroundInfluentialSelf-citationIL-6 pathway in the liver: From physiopathology to therapy
Schmidt-Arras, D., & Rose-John, S. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.02.004 · Cited by 881
Self-citationIL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation
Kaplanski, G. (2003) · Trends in Immunology · doi:10.1016/s1471-4906(02)00013-3 · Cited by 811
Hurst, S. M., Wilkinson, T. S., McLoughlin, R. M., Jones, S., Horiuchi, S., Yamamoto, N., Rose-John, S., Fuller, G. M., Topley, N., & Jones, S. A. (2001) · Immunity · doi:10.1016/s1074-7613(01)00151-0 · Cited by 811
Self-citationMaes, M., Meltzer, H. Y., Bosmans, E., Bergmans, R., Vandoolaeghe, E., Ranjan, R., & Desnyder, R. (1995) · Journal of Affective Disorders · doi:10.1016/0165-0327(95)00028-l · Cited by 622
Interleukin-6 and its receptors: a highly regulated and dynamic system
Wolf, J., Rose-John, S., & Garbers, C. (2014) · Cytokine · doi:10.1016/j.cyto.2014.05.024 · Cited by 618
Self-citationTargeting IL-6 trans-signalling: past, present and future prospects
Rose-John, S., Jenkins, B. J., Garbers, C., Moll, J. M., & Scheller, J. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00856-y · Cited by 524
Self-citationThe role of interleukin-6 signaling in nervous tissue
Rothaug, M., Becker-Pauly, C., & Rose-John, S. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.03.018 · Cited by 491
Matthews, V., Schuster, B., Schütze, S., Bussmeyer, I., Ludwig, A., Hundhausen, C., Sadowski, T., Saftig, P., Hartmann, D., Kallen, K.-J., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210584200 · Cited by 390
Self-citationInterleukin-6, a mental cytokine
Spooren, A., Kolmus, K., Laureys, G., Clinckers, R., De Keyser, J., Haegeman, G., & Gerlo, S. (2011) · Brain Research Reviews · doi:10.1016/j.brainresrev.2011.01.002 · Cited by 352
Kern, L., Mittenbühler, M., Vesting, A., Ostermann, A., Wunderlich, C., & Wunderlich, F. (2018) · Cancers · doi:10.3390/cancers11010024 · Cited by 331
Interleukin-6: from basic biology to selective blockade of pro-inflammatory activities
Scheller, J., Garbers, C., & Rose-John, S. (2014) · Seminars in Immunology · doi:10.1016/j.smim.2013.11.002 · Cited by 308
Self-citationIntegrating Interleukin-6 into depression diagnosis and treatment
Hodes, G. E., Ménard, C., & Russo, S. J. (2016) · Neurobiology of Stress · doi:10.1016/j.ynstr.2016.03.003 · Cited by 271
Baran, P., Hansen, S., Waetzig, G. H., Akbarzadeh, M., Lamertz, L., Huber, H. J., Ahmadian, M. R., Moll, J. M., & Scheller, J. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.001163 · Cited by 235
Reeh, H., Rudolph, N., Billing, U., Christen, H., Streif, S., Bullinger, E., Schliemann-Bullinger, M., Findeisen, R., Schaper, F., Huber, H. J., et al. (2019) · Cell Communication and Signaling · doi:10.1186/s12964-019-0356-0 · Cited by 180
The soluble interleukin 6 receptor: advanced therapeutic options in inflammation
Rose‐John, S. (2017) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.782 · Cited by 169
Self-citationSoluble interleukin-6 (IL-6) receptor augments central effects of IL-6 in vivo.
Schöbitz, B., Pezeshki, G., Pohl, T., Hemmann, U., Heinrich, P. C., Holsboer, F., & Reul, J. M. H. M. (1995) · The FASEB Journal · doi:10.1096/fasebj.9.8.7768358 · Cited by 159
Self-citationGarbers, C., Monhasery, N., Aparicio-Siegmund, S., Lokau, J., Baran, P., Nowell, M. A., Jones, S. A., Rose-John, S., & Scheller, J. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.05.018 · Cited by 155
Self-citationRole of Interleukin-6 in Vascular Health and Disease
Villar-Fincheira, P., Sanhueza-Olivares, F., Norambuena-Soto, I., Cancino-Arenas, N., Hernandez-Vargas, F., Troncoso, R., Gabrielli, L., & Chiong, M. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.641734 · Cited by 154
New insights into IL-6 family cytokines in metabolism, hepatology and gastroenterology
Giraldez, M. D., Carneros, D., Garbers, C., Rose-John, S., & Bustos, M. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00473-x · Cited by 156
Self-citationHarbour, S. N., DiToro, D. F., Witte, S. J., Zindl, C. L., Gao, M., Schoeb, T. R., Jones, G. W., Jones, S. A., Hatton, R. D., & Weaver, C. T. (2020) · Science Immunology · doi:10.1126/sciimmunol.aaw2262 · Cited by 151
Combined interleukin 6 and soluble interleukin 6 receptor accelerates murine liver regeneration
Peters, M., Blinn, G., Jostock, T., Schirmacher, P., Büschenfelde, K. M. Z., Galle, P. R., & Rose–John, S. (2000) · Gastroenterology · doi:10.1053/gast.2000.20236 · Cited by 129
Self-citationMaes, M., Ombelet, W., De Jongh, Kenis, G., & Bosmans, E. (2001) · Journal of Affective Disorders · doi:10.1016/s0165-0327(00)00156-7 · Cited by 116
Interleukin-6 expression after renal transplantation
Waiser, J., Budde, K., Katalinic, A., Kuerzdorfer, M., Riess, R., & Neumayer, H. H. (1997) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/12.4.753 · Cited by 79
Molecular insights into the multilayered regulation of ADAM17: The role of the extracellular region
Grötzinger, J., Lorenzen, I., & Düsterhöft, S. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2017.05.024 · Cited by 76
Targeting IL-6 or IL-6 Receptor in Rheumatoid Arthritis: What Have We Learned?
Avci, A. B., Feist, E., & Burmester, G. R. (2024) · BioDrugs · doi:10.1007/s40259-023-00634-1 · Cited by 50
The Regenerative Activity of Interleukin-6
Galun, E., & Rose-John, S. (2013) · Methods in Molecular Biology · doi:10.1007/978-1-62703-308-4_4 · Cited by 34
Self-citationSoluble LDL‐R are formed by cell surface cleavage in response to phorbol esters
Begg, M. J., Sturrock, E. D., & van der Westhuyzen, D. R. (2004) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03953.x · Cited by 24
Robak, T., Wierzbowska, A., Błasińska-Morawiec, M., Korycka, A., & Błoński, J. Z. (1999) · Mediators of Inflammation · doi:10.1080/09629359990289 · Cited by 20
Mittenbühler, M. J., Sprenger, H.-G., Gruber, S., Wunderlich, C. M., Kern, L., Brüning, J. C., & Wunderlich, F. T. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.08.010 · Cited by 18
Metadata
- Authors
- Mülberg, J., Schooltink, H., Stoyan, T., Günther, M., Graeve, L., Buse, G., Mackiewicz, A., Heinrich, P. C., & Rose‐John, S.
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 1993-02
- Volume
- 23
- Issue
- 2
- Pages
- 473-480
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W2046396043
- Cited by
- 506
- References
- 1
- FWCI
- 9.51
- Type
- journal article
- Language
- en
- Open access
- closed
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