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The function of the soluble interleukin 6 (IL-6) receptor in vivo: sensitization of human soluble IL-6 receptor transgenic mice towards IL-6 and prolongation of the plasma half-life of IL-6.
Open accessAbstract
Interleukin 6 (IL-6) is considered an important mediator of acute inflammatory responses. Moreover, IL-6 functions as a differentiation and growth factor of hematopoietic precursor cells, B cells, T cells, keratinocytes, neuronal cells, osteoclasts, and endothelial cells. IL-6 exhibits its action via a receptor complex consisting of a specific IL-6 receptor (IL-6R) and a signal transducing subunit (gp130). Soluble forms of both receptor components are generated by shedding and are found in patients with various diseases such as acquired immune deficiency syndrome, rheumatoid arthritis, and others. The function of the soluble (s)IL-6R in vivo is unknown. Since human (h)IL-6 acts on human and murine target cells, but murine IL-6 on murine cells only, we constructed transgenic mice expressing the hsIL-6R. We report here that in the presence of hsIL-6R, mice are hypersensitized towards hIL-6, mounting an acute phase protein gene induction at significantly lower IL-6 dosages compared to control animals. Furthermore, in hsIL-6R transgenic mice, the detected acute phase response persists for a longer period of time. The IL-6/IL-6R complex prolongs markedly the Il-6 plasma half-life. Our results reinforce the role of the hsIL-6R as an agonistic protein, help to understand the function of the hsIL-6R in vivo, and highlight the significance of the receptor in the induction of the acute phase response.
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TURNBULL, A. V., & RIVIER, C. L. (1999) · Physiological Reviews · doi:10.1152/physrev.1999.79.1.1 · Cited by 1,297
Atreya, R., Mudter, J., Finotto, S., Müllberg, J., Jostock, T., Wirtz, S., Schütz, M., Bartsch, B., Holtmann, M., Becker, C., et al. (2000) · Nature Medicine · doi:10.1038/75068 · Cited by 1,293
Self-citation(2012) · The Lancet · doi:10.1016/s0140-6736(12)60110-x · Cited by 1,146
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Papanicolaou, D. A., Wilder, R. L., Manolagas, S. C., & Chrousos, G. P. (1998) · Annals of Internal Medicine · doi:10.7326/0003-4819-128-2-199801150-00009 · Cited by 1,146
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Rose-John, S. (2012) · International Journal of Biological Sciences · doi:10.7150/ijbs.4989 · Cited by 1,040
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Self-citationNicklas, B. J., Ambrosius, W., Messier, S. P., Miller, G. D., Penninx, B. W., Loeser, R. F., Palla, S., Bleecker, E., & Pahor, M. (2004) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/79.4.544 · Cited by 443
Maes, M., Lin, A.-H., Delmeire, L., Van Gastel, A., Kenis, G., De Jongh, R., & Bosmans, E. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00131-0 · Cited by 387
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Self-citationShariat, S. F., Andrews, B., Kattan, M. W., Kim, J., Wheeler, T. M., & Slawin, K. M. (2001) · Urology · doi:10.1016/s0090-4295(01)01405-4 · Cited by 261
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Klein, C., Wüstefeld, T., Assmus, U., Roskams, T., Rose-John, S., Müller, M., Manns, M. P., Ernst, M., & Trautwein, C. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200523640 · Cited by 200
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Giuliani, N., Sansoni, P., Girasole, G., Vescovini, R., Passeri, G., Passeri, M., & Pedrazzoni, M. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00220-5 · Cited by 151
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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
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Galun, E., Zeira, E., Pappo, O., Peters, M., & Rose-John, S. (2000) · The FASEB Journal · doi:10.1096/fj.99-0913com · Cited by 124
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CHENG, C. M., COHEN, M., WANG, J., & BONDY, C. A. (2001) · The FASEB Journal · doi:10.1096/fj.00-0398com · Cited by 115
Tsukamoto, H., Senju, S., Matsumura, K., Swain, S. L., & Nishimura, Y. (2015) · Nature Communications · doi:10.1038/ncomms7702 · Cited by 104
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Rodríguez-Bayona, B., Ramos-Amaya, A., López-Blanco, R., Campos-Caro, A., & Brieva, J. A. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1301559 · Cited by 53
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Self-citation
Metadata
- Authors
- Peters, M., Jacobs, S., Ehlers, M., Vollmer, P., Müllberg, J., Wolf, E., Brem, G., Meyer zum Büschenfelde, K. H., & Rose-John, S.
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1996-04-01
- Volume
- 183
- Issue
- 4
- Pages
- 1399-1406
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2107682360
- Cited by
- 276
- References
- 0
- FWCI
- 5.41
- Type
- journal article
- Language
- en
- Open access
- bronze
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