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Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer
Abstract
Cytokine receptors, which exist in membrane-bound and soluble forms, bind their ligands with comparable affinity. Although most soluble receptors are antagonists and compete with their membrane-associated counterparts for the ligands, certain soluble receptors are agonists. In these cases, complexes of ligand and soluble receptor bind on target cells to second receptor subunits and initiate intracellular signaling. The soluble receptors of the interleukin (IL)-6 family of cytokines (sIL-6R, sIL-11R, soluble ciliary neurotrophic factor receptor) are agonists capable of transmitting signals through interaction with the universal signal-transducing receptor for all IL-6 family cytokines, gp130. In vivo, the IL-6/sIL-6R complex stimulates several types of cells, which are unresponsive to IL-6 alone, as they do not express the membrane IL-6R. We have named this process trans-signaling. The generation of soluble cytokine receptors occurs via two distinct mechanisms—limited proteolysis and translation—from differentially spliced mRNA. We have demonstrated that a soluble form of the IL-6 family signaling receptor subunit gp130, which is generated by differential splicing, is the natural inhibitor of IL-6 trans-signaling responses. We have shown that in many chronic inflammatory diseases, including chronic inflammatory bowel disease, peritonitis, rheumatoid arthritis, asthma, as well as colon cancer, IL-6 trans-signaling is critically involved in the maintenance of a disease state, by promoting transition from acute to chronic inflammation. Moreover, in all these models, the course of the disease can be disrupted by specifically interfering with IL-6 trans-signaling using the soluble gp130 protein. The pathophysiological mechanisms by which the IL-6/sIL-6R complex regulates the inflammatory state are discussed.
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Citations
Cites
IL-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
Interleukin (IL)-6 directs the differentiation of IL-4-producing CD4+ T cells
Rincón, M., Anguita, J., Nakamura, T., Fikrig, E., & Flavell, R. A. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.3.461 · Cited by 810
Ito, H., Takazoe, M., Fukuda, Y., Hibi, T., Kusugami, K., Andoh, A., Matsumoto, T., Yamamura, T., Azuma, J., & Nishimoto, N. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.01.012 · Cited by 636
IL-6 is required for the development of Th1 cell-mediated murine colitis
Yamamoto, M., Yoshizaki, K., Kishimoto, T., & Ito, H. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.9.4878 · Cited by 411
Interleukin 6 plays a key role in the development of antigen-induced arthritis
Ohshima, S., Saeki, Y., Mima, T., Sasai, M., Nishioka, K., Nomura, S., Kopf, M., Katada, Y., Tanaka, T., Suemura, M., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.8222 · Cited by 406
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-citationMadhok, R., Crilly, A., Watson, J., & Capell, H. A. (1993) · Annals of the Rheumatic Diseases · doi:10.1136/ard.52.3.232 · Cited by 340
Jenkins, B. J., Grail, D., Nheu, T., Najdovska, M., Wang, B., Waring, P., Inglese, M., McLoughlin, R. M., Jones, S. A., Topley, N., et al. (2005) · Nature Medicine · doi:10.1038/nm1282 · Cited by 308
Self-citation
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Targeting the IL-6/JAK/STAT3 signalling axis in cancer
Johnson, D. E., O'Keefe, R. A., & Grandis, J. R. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2018.8 · Cited by 3,110
A cytokine-mediated link between innate immunity, inflammation, and cancer
Lin, W.-W., & Karin, M. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31537 · Cited by 1,940
Rose-John, S. (2012) · International Journal of Biological Sciences · doi:10.7150/ijbs.4989 · Cited by 1,040
“These results indicated that the IL-6 trans-signaling pathway was used in many cell types and tissues [53].”
BackgroundSelf-citationLesina, M., Kurkowski, M. U., Ludes, K., Rose-John, S., Treiber, M., Klöppel, G., Yoshimura, A., Reindl, W., Sipos, B., Akira, S., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.03.009 · Cited by 862
Self-citationYokota, S., Imagawa, T., Mori, M., Miyamae, T., Aihara, Y., Takei, S., Iwata, N., Umebayashi, H., Murata, T., Miyoshi, M., et al. (2008) · The Lancet · doi:10.1016/s0140-6736(08)60454-7 · Cited by 789
Interleukin‐6 myokine signaling in skeletal muscle: a double‐edged sword?
Muñoz‐Cánoves, P., Scheele, C., Pedersen, B. K., & Serrano, A. L. (2013) · The FEBS Journal · doi:10.1111/febs.12338 · Cited by 774
Sansone, P., Storci, G., Tavolari, S., Guarnieri, T., Giovannini, C., Taffurelli, M., Ceccarelli, C., Santini, D., Paterini, P., Marcu, K. B., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32533 · Cited by 779
The wolf in sheep's clothing: the role of interleukin-6 in immunity, inflammation and cancer
Naugler, W. E., & Karin, M. (2008) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.12.007 · Cited by 730
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-citationThe ADAMs: signalling scissors in the tumour microenvironment
Murphy, G. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2459 · Cited by 451
Li, Y., de Haar, C., Chen, M., Deuring, J., Gerrits, M. M., Smits, R., Xia, B., Kuipers, E. J., & van der Woude, C. J. (2010) · Gut · doi:10.1136/gut.2009.184176 · Cited by 339
Wei, H., Zou, H., Sheikh, A. M., Malik, M., Dobkin, C., Brown, W. T., & Li, X. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-52 · Cited by 333
Role of interleukin-6 in stress, sleep, and fatigue
Rohleder, N., Aringer, M., & Boentert, M. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06634.x · Cited by 289
IL-6 regulation of synaptic function in the CNS
Gruol, D. L. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.10.023 · Cited by 254
Differences in Wound Healing in Mice with Deficiency of IL-6 versus IL-6 Receptor
McFarland-Mancini, M. M., Funk, H. M., Paluch, A. M., Zhou, M., Giridhar, P. V., Mercer, C. A., Kozma, S. C., & Drew, A. F. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0901929 · Cited by 249
Environmental immune disruptors, inflammation and cancer risk
Thompson, P. A., Khatami, M., Baglole, C. J., Sun, J., Harris, S. A., Moon, E.-Y., Al-Mulla, F., Al-Temaimi, R., Brown, D. G., Colacci, A. M., et al. (2015) · Carcinogenesis · doi:10.1093/carcin/bgv038 · Cited by 227
Nowell, M. A., Williams, A. S., Carty, S. A., Scheller, J., Hayes, A. J., Jones, G. W., Richards, P. J., Slinn, S., Ernst, M., Jenkins, B. J., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.182.1.613 · Cited by 215
Self-citationJones, G. W., McLoughlin, R. M., Hammond, V. J., Parker, C. R., Williams, J. D., Malhotra, R., Scheller, J., Williams, A. S., Rose-John, S., Topley, N., et al. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0901528 · Cited by 189
Self-citationBarkhausen, T., Tschernig, T., Rosenstiel, P., van Griensven, M., Vonberg, R.-P., Dorsch, M., Mueller-Heine, A., Chalaris, A., Scheller, J., Rose-John, S., et al. (2011) · Critical Care Medicine · doi:10.1097/ccm.0b013e318211ff56 · Cited by 169
Self-citationInflammation and cortisol response in coronary artery disease
Nijm, J., & Jonasson, L. (2009) · Annals of Medicine · doi:10.1080/07853890802508934 · Cited by 128
IL-17RC: a partner in IL-17 signaling and beyond
Ho, A. W., & Gaffen, S. L. (2010) · Seminars in Immunopathology · doi:10.1007/s00281-009-0185-0 · Cited by 104
The combined role of serotonin and interleukin-6 as biomarker for autism
Yang, C.-J., Liu, C.-L., Sang, B., Zhu, X.-M., & Du, Y.-J. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2014.10.011 · Cited by 80
Dalgård, C., Nielsen, F., Morrow, J. D., Enghusen-Poulsen, H., Jonung, T., Hørder, M., & de Maat, M. P. M. (2008) · British Journal Of Nutrition · doi:10.1017/s0007114508995660 · Cited by 78
Tsukamoto, H., Fujieda, K., Hirayama, M., Ikeda, T., Yuno, A., Matsumura, K., Fukuma, D., Araki, K., Mizuta, H., Nakayama, H., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2446 · Cited by 53
TGF-β1 Limits the Onset of Innate Lung Inflammation by Promoting Mast Cell–Derived IL-6
Ganeshan, K., Johnston, L. K., & Bryce, P. J. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1203362 · Cited by 45
Role of IL-6 trans-signaling in CCl4 induced liver damage
Gewiese-Rabsch, J., Drucker, C., Malchow, S., Scheller, J., & Rose-John, S. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.07.023 · Cited by 36
Self-citationThe 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-citationShriki, A., Lanton, T., Sonnenblick, A., Levkovitch-Siany, O., Eidelshtein, D., Abramovitch, R., Rosenberg, N., Pappo, O., Elgavish, S., Nevo, Y., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-21-0321 · Cited by 34
Self-citationRole of interleukin‐6 and pentraxin 3 as an early marker in Peyronie's disease
Atar, A., Kural, A., Yenice, G., Comez, I., & Tugcu, V. (2017) · The Kaohsiung Journal of Medical Sciences · doi:10.1016/j.kjms.2017.01.007 · Cited by 11
“The IL-6/IL-6 soluble receptor/glycoprotein 130 complex have a significant role in the inflammatory pathways of various autoimmune diseases such as chronic inflammatory bowel disease, rheumatoid arthritis, and asthma [6,7].”
BackgroundNystuen, A., Gonzalez-Lopez, E., Kauper, K. A., Eade, K., & Aaberg, T. M. (2025) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2025.06.005 · Cited by 11
Metadata
- Authors
- Rose-John, S., Scheller, J., Elson, G., & Jones, S. A.
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-05-17
- Volume
- 80
- Issue
- 2
- Pages
- 227-236
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W2101596544
- Cited by
- 647
- References
- 8
- FWCI
- 18.45
- Type
- journal article
- Language
- en
- Open access
- closed
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