Impact of interleukin-6 classic- and trans-signaling on liver damage and regeneration
Abstract
Interleukin-6 (IL-6) has been suggested to play a pivotal role in liver regeneration. IL-6 on target cells activates a receptor complex consisting of the IL-6 receptor (IL-6R) and the signal transducing receptor subunit gp130. Not all cells in the body express the IL-6R on the cell surface. IL-6 can signal via two different pathways: classical signaling via the membrane bound IL-6R and IL-6 trans-signaling via a naturally occurring soluble IL-6R (sIL-6R). This second pathway widens the scope of IL-6 signaling since also cells expressing no membrane bound IL-6R can be stimulated by the trans-signal pathway. Mimicking IL-6 trans-signaling via a designer molecule, Hyper-IL-6 has been shown to accelerate liver regeneration. Another designer molecule, sgp130Fc, specifically blocks IL-6 trans-signaling. Using these proteins we investigated the contribution of IL-6 classic- and trans-signaling in the liver. Here we review the role of IL-6 signaling in response to liver damage and during liver regeneration.
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The critical role of the IL-6/IL-6R/gp130-JAK-STAT3 axis is well-established in the initiation phase of liver regeneration after partial hepatectomy.
“The critical role of the IL-6/IL-6R/gp130-JAK-STAT3 axis has been well-established in the initiation phase of liver regeneration after partial hepatectomy (Fig. 2) [15, 16].”
From The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases (2024) · cites this paper as [15]
Cites
Liver Failure and Defective Hepatocyte Regeneration in Interleukin-6-Deficient Mice
Cressman, D. E., Greenbaum, L. E., DeAngelis, R. A., Ciliberto, G., Furth, E. E., Poli, V., & Taub, R. (1996) · Science · doi:10.1126/science.274.5291.1379 · Cited by 1,536 · see citing works
Mizuhara, H., O'Neill, E., Seki, N., Ogawa, T., Kusunoki, C., Otsuka, K., Satoh, S., Niwa, M., Senoh, H., & Fujiwara, H. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.5.1529 · Cited by 517 · see citing works
Increased toxin-induced liver injury and fibrosis in interleukin-6-deficient mice
Kovalovich, K., DeAngelis, R. A., Li, W., Furth, E. E., Ciliberto, G., & Taub, R. (2000) · Hepatology · doi:10.1002/hep.510310123 · Cited by 298 · see citing works
Interleukin 6 Is Important for Survival After Partial Hepatectomy in Mice
Blindenbacher, A., Wang, X., Langer, I., Savino, R., Terracciano, L., & Heim, M. H. (2003) · Hepatology · doi:10.1053/jhep.2003.50378 · Cited by 202 · see citing works
Trautwein, C., Rakemann, T., Niehof, M., Rose-John, S., & Manns, M. (1996) · Gastroenterology · doi:10.1053/gast.1996.v110.pm8964411 · Cited by 131 · see citing works
Self-citationCombined 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 · see citing works
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IL-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 · see citing works
Self-citationNew 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 · see citing works
Self-citationEbihara, N., Matsuda, A., Nakamura, S., Matsuda, H., & Murakami, A. (2011) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.11-7956 · Cited by 147 · see citing works
The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases
Wang, M.-J., Zhang, H.-L., Chen, F., Guo, X.-J., Liu, Q.-G., & Hou, J. (2024) · Experimental Hematology & Oncology · doi:10.1186/s40164-024-00527-1 · Cited by 84 · see citing works
“2) [15, 16].”
Naseem, S., Hussain, T., & Manzoor, S. (2018) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2018.01.002 · Cited by 72 · see citing works
- Authors
- Drucker, C., Gewiese, J., Malchow, S., Scheller, J., & Rose-John, S.
- Affiliations
- Christian-Albrechts-Universität zu Kiel (DE)
- ORCID
- Scheller, Jürgen
- Venue
- Journal of Autoimmunity
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 34
- Issue
- 1
- Pages
- 29-37
- ISSN
- 0896-8411 (ISSN-L)
- OpenAlex
- W2055253557
- Cited by
- 83
- References
- 6
- Citations by year
- 2025: 2 · 2024: 5 · 2023: 2 · 2022: 6 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 6 · 2016: 8 · 2015: 5 · 2014: 6 · 2013: 8 · 2012: 7
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Autoimmunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Keywords
- interleukin-6, IL-6 trans-signaling, soluble IL-6 receptor, gp130, liver regeneration, liver injury, hyper-IL-6, sgp130Fc, cytokine signaling
- MeSH terms
- Animals, Antibodies, Monoclonal, Arthritis, Rheumatoid, Humans, Liver, Liver Regeneration, Signal Transduction, Interleukin-6, Apoptosis, Receptors, Interleukin-6, Cytokine Receptor gp130, Antibodies, Monoclonal, Humanized
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