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IL-6 Trans-Signaling via the Soluble IL-6 Receptor: Importance for the Pro-Inflammatory Activities of IL-6
Open accessAbstract
Interleukin-6 (IL-6) is a cytokine with many activities. It has functions in the regulation of the immune system and the nervous system. Furthermore, IL-6 is involved in liver regeneration and in the metabolic control of the body. On target cells, IL-6 binds to an 80 kDa IL-6 receptor (IL-6R). The complex of IL-6 and IL-6R associates with a second protein, gp130, which thereupon dimerizes and initiates intracellular signaling. Whereas gp130 is expressed on all cells, IL-6R is only present on few cells in the body including hepatocytes and some leukocytes. Cells, which do not express IL-6R cannot respond to the cytokine, since gp130 alone has no measurable affinity for IL-6. Interestingly, a soluble form of IL-6R (sIL-6R) comprising the extracellular portion of the receptor can bind IL-6 with a similar affinity as the membrane bound IL-6R. The complex of IL-6 and sIL-6R can bind to gp130 on cells, which do not express the IL-6R, and which are unresponsive to IL-6. This process has been called trans-signaling. Here I will review published evidence that IL-6 trans-signaling is pro-inflammatory whereas classic IL-6 signaling via the membrane bound IL-6R is needed for regenerative or anti-inflammatory activities of the cytokine. Furthermore, the detailed knowledge of IL-6 biology has important consequences for therapeutic strategies aimed at the blockade of the cytokine IL-6.
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“Therefore, the balance between mbIL-6R and sIL-6R availability, along with signal duration and tissue context, determines whether IL-6 acts in a protective or pathogenic manner [40].”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [40]
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“HyIL-6 triggers signaling in all cells expressing gp130, producing a more robust and homogenous signaling output”
From CDK8 fine-tunes IL-6 transcriptional activities by limiting STAT3 resident time at the gene loci (2020) · cites this paper as Rose-John, 2012
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“This is in line with the view that classic and trans-signaling promote anti- and pro-inflammatory responses, respectively (85)”
From T H 17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity (2020) · cites this paper as [85]
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Interleukin-6 and Soluble Interleukin-6 Receptor: Direct Stimulation of gp130 and Hematopoiesis
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MethodSelf-citationC-reactive Protein: A Physiological Activator of Interleukin 6 Receptor Shedding
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“As recently reported, the sgp130Fc protein under conditions, when sIL-6R levels largely exceed levels of IL-6, can also block IL-6 classic signaling because then free IL-6 will bind to the excess of sIL-6R and this complex will bind to and will be neutralized by sgp130Fc [70].”
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“It was shown that this local regulation of sIL-6R activity and IL-6 trans-signaling contributes to the status of the T-cell response [31].”
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“Activities of IL-6 can be regenerative and protective during infection and inflammation [76, 77, 96].”
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Self-citationCutting Edge: Soluble IL-6R Is Produced by IL-6R Ectodomain Shedding in Activated CD4 T Cells
Briso, E. M., Dienz, O., & Rincón, M. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.11.7102 · Cited by 165 · cited 1×
“Interestingly, sIL-6R is produced by naïve and memory CD4-T-cells when the T-cell receptor is activated [30].”
BackgroundAudet, J., Miller, C., Rose‐John, S., Piret, J. M., & Eaves, C. J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.4.1757 · Cited by 137
Self-citationSuthaus, J., Stuhlmann-Laeisz, C., Tompkins, V., Rosean, T. R., Klapper, W., Tosato, G., Janz, S., Scheller, J., & Rose-John, S. (2012) · Blood · doi:10.1182/blood-2011-09-377705 · Cited by 131 · cited 2×
“Furthermore, in mice transgenic for vIL-6 we observed development of a phenotype, which closely resembled multicentric Castleman disease [93].”
BackgroundSelf-citationMaione, D., Carlo, E. D., Li, W., Musiani, P., Modesti, A., Peters, M., Rose‐John, S., Rocca, C. D., Tripodi, M., Lazzaro, D., et al. (1998) · The EMBO Journal · doi:10.1093/emboj/17.19.5588 · Cited by 128 · cited 1×
“It turned out that only double transgenic IL-6/sIL-6R mice showed massive extramedullary hematopoiesis [40] together with hepatocellular proliferation [41, 42].”
BackgroundSelf-citationDevelopment of progressive kidney damage and myeloma kidney in interleukin-6 transgenic mice
Fattori, E., Rocca, C. D., Costa, P., Giorgio, M., Dente, B., Pozzi, L., & Ciliberto, G. (1994) · Blood · doi:10.1182/blood.v83.9.2570.2570 · Cited by 124
STAT3 activation via interleukin 6 trans-signalling contributes to ileitis in SAMP1/Yit mice
Mitsuyama, K., Matsumoto, S., Rose‐John, S., Suzuki, A., Hara, T., Tomiyasu, N., Handa, K., Tsuruta, O., Funabashi, H., Scheller, J., et al. (2006) · Gut · doi:10.1136/gut.2005.079343 · Cited by 120 · cited 1×
“Intestinal Inflammation DSS-colitis, SAMP/YIT mouse model [98, 99]”
Self-citationDifferential shedding of the two subunits of the interleukin‐6 receptor
Müllberg, J., Dittrich, E., Graeve, L., Gerhartz, C., Yasukawa, K., Taga, T., Kishimoto, T., Heinrich, P. C., & Rose‐John, S. (1993) · FEBS Letters · doi:10.1016/0014-5793(93)80507-q · Cited by 116 · cited 1×
“The soluble forms of sgp130 were found not to be generated by proteolytic cleavage [35] but rather by translation from alternatively spliced mRNA [36].”
BackgroundSelf-citationProtein kinase C activity is rate limiting for shedding of the interleukin-6 receptor
Müllberg, J., Schooltink, H., Stoyan, T., Heinrich, P. C., & Rose‐John, S. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)92272-y · Cited by 116 · cited 1×
“Stimulation of the cells with the phorbol ester PMA induced complete loss of the IL-6R from the cell surface within 1 h [14, 20].”
BackgroundSelf-citationSleep enhances IL‐6 trans‐signaling in humans
Dimitrov, S., Lange, T., Benedict, C., Nowell, M. A., Jones, S. A., Scheller, J., Rose‐John, S., Born, J., Dimitrov, S., Lange, T., et al. (2006) · The FASEB Journal · doi:10.1096/fj.06-5754fje · Cited by 115 · cited 1×
“It is thought that regulated generation of the sIL-6R occurs through shedding rather than through differential splicing [16].”
BackgroundSelf-citationvan Dam, M., Müllberg, J., Schooltink, H., Stoyan, T., Brakenhoff, J. P. J., Graeve, L., Heinrich, P. C., & Rose‐John, S. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82467-x · Cited by 113
Self-citationIL-6 Receptor Independent Stimulation of Human gp130 by Viral IL-6
Müllberg, J., Geib, T., Jostock, T., Hoischen, S. H., Vollmer, P., Voltz, N., Heinz, D. W., Galle, P. R., Klouche, M., & Rose‐John, S. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.9.4672 · Cited by 110
Self-citationStudies on the structure and regulation of the human hepatic interleukin‐6 receptor
Rose‐John, S., Schooltink, H., Lenz, D., Erich, H. I. P. P., Dufhues, G., SCHMITZ, H., Schiel, X., Hirano, T., Kishimoto, T., & Heinrich, P. C. (1990) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1990.tb15548.x · Cited by 108 · cited 1×
“This could be explained by the fact that the affinity of IL-6 to IL-6R is in the range of 1 nM whereas the complex of IL-6/IL-6R binds with 100 times higher affinity to gp130 [46].”
BackgroundSelf-citationIn Vivo and In Vitro Activities of the gp130-Stimulating Designer Cytokine Hyper-IL-6
Peters, M., Blinn, G., Solem, F. K., Fischer, M., Büschenfelde, K. M. Z., & Rose‐John, S. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.7.3575 · Cited by 104
Self-citationPore-forming toxins trigger shedding of receptors for interleukin 6 and lipopolysaccharide.
Walev, I., Vollmer, P., Palmer, M., Bhakdi, S., & Rose‐John, S. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.15.7882 · Cited by 102 · cited 1×
“Subsequent studies established that treatment of cells with C-reactive protein (CRP) [22], bacterial toxins [23] and cholesterol depleting agents [24] as well as treatment of cells with bacterial metalloproteinases [25] induced shedding of the IL-6R.”
BackgroundSelf-citationRichards, P. J., Nowell, M. A., Horiuchi, S., McLoughlin, R. M., Fielding, C. A., Grau, S., Yamamoto, N., Ehrmann, M., Rose‐John, S., Williams, A. S., et al. (2006) · Arthritis & Rheumatism · doi:10.1002/art.21818 · Cited by 99 · cited 2×
“It was shown that like the soluble, entire extracellular form of sgp130, the shorter form gp130-RAPS could bind the IL-6/sIL-6R complex [34].”
BackgroundSelf-citationVollmer, P., Walev, I., Rose‐John, S., & Bhakdi, S. (1996) · Infection and Immunity · doi:10.1128/iai.64.9.3646-3651.1996 · Cited by 98 · cited 1×
“Subsequent studies established that treatment of cells with C-reactive protein (CRP) [22], bacterial toxins [23] and cholesterol depleting agents [24] as well as treatment of cells with bacterial metalloproteinases [25] induced shedding of the IL-6R.”
BackgroundSelf-citationInterleukin‐6 serum levels in patients with gynecological tumors
Scambia, G., Testa, U., Panici, P. B., Martucci, R., Foti, E., Petrini, M., Amoroso, M., Masciullo, V., Peschle, C., & Mancuso, S. (1994) · International Journal of Cancer · doi:10.1002/ijc.2910570305 · Cited by 93 · cited 1×
“In healthy subjects, IL-6 plasma levels are barely detectable and range between 2-6 pg/ml [62].”
BackgroundViswanathan, S., Benatar, T., Rose‐John, S., Lauffenburger, D. A., & Zandstra, P. W. (2002) · Stem Cells · doi:10.1634/stemcells.20-2-119 · Cited by 92 · cited 1×
“Cells, which would only respond to IL-6 in the presence of the sIL-6R include hematopoietic stem cells [47], many if not all neural cells [48, 49], smooth muscle cells [50] and embryonic stem cells [51, 52].”
BackgroundSelf-citationDittrich, E., Rose‐John, S., Gerhartz, C., Müllberg, J., Stoyan, T., Yasukawa, K., Heinrich, P. C., & Graeve, L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32267-6 · Cited by 91
Self-citationVirokines in the Pathogenesis of Cancer: Focus on Human Herpesvirus 8
Klouche, M., Carruba, G., CASTAGNETTA, L. A. M., & Rose‐John, S. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1322.038 · Cited by 91 · cited 1×
“Since vIL-6 is the only known cytokine, which can stimulate gp130 without the help of an additional receptor protein, we speculated that vIL-6 was a natural model for IL-6 trans-signaling [89-91].”
BackgroundSelf-citationPadberg, F., Feneberg, W. W., Schmidt, S., Schwarz, M., Körschenhausen, D. A., Greenberg, B. D., Nolde, T., Müller, N., Trapmann, H., König, N., et al. (1999) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(99)00120-4 · Cited by 88
Schirmacher, P., Peters, M., Ciliberto, G., Blessing, M., Lotz, J., Büschenfelde, K. M. Z., & Rose‐John, S. (1998) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65605-2 · Cited by 87
Self-citationHitting a complex target: an update on interleukin-6 trans-signalling
Waetzig, G. H., & Rose‐John, S. (2012) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2012.660307 · Cited by 83 · cited 2×
“These experiments allowed to decide whether the gp130 driven disease model was based on IL-6 classic signaling or IL-6 trans-signaling [54, 55].”
BackgroundMethodSelf-citationDimerization of the cytokine receptors gp130 and LIFR analysed in single cells
Giese, B., Roderburg, C., Sommerauer, M., Wortmann, S. B., Metz, S., Heinrich, P. C., & Müller‐Newen, G. (2005) · Journal of Cell Science · doi:10.1242/jcs.02628 · Cited by 81 · cited 2×
“The dimerization of gp130 found in the absence of receptor stimulation [57, 58] apparently does not position the transmembrane domains and cytoplasmic domains of gp130 in a way that is sufficient to induce gp130 signaling.”
BackgroundADAM17-mediated shedding of the IL6R induces cleavage of the membrane stub by γ-secretase
Chalaris, A., Gewiese, J., Paliga, K., Fleig, L., Schneede, A., Krieger, K., Rose‐John, S., & Scheller, J. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2009.12.001 · Cited by 75 · cited 1×
“Since shedding of the IL-6R is mainly governed by the protease ADAM17 [14, 80], we speculate that ADAM17 has a decisive role in inflammation and cancer [17] (Fig.”
BackgroundSelf-citationStuhlmann-Laeisz, C. M., Lang, S., Chalaris, A., Paliga, K., Sudarman, E., Eichler, J., Klingmüller, U., Samuel, M. S., Ernst, M., Rose‐John, S., et al. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-12-1129 · Cited by 72 · cited 3×
“To address this question a gp130 cDNA was constructed, in which the entire region coding for the extracellular portion was replaced by DNA sequences coding for the leucine-zipper from the Jun protein [59, 60].”
BackgroundMethodSelf-citationThe interleukin 6 pathway and atherosclerosis
Scheller, J., & Rose‐John, S. (2012) · The Lancet · doi:10.1016/s0140-6736(12)61246-x · Cited by 68
Self-citationTGF-beta suppresses tumor progression in colon cancer by inhibition of IL–6 trans-signaling
Becker, C., Fantini, M. C., Schramm, C., Lehr, H., Wirtz, S. J., Becker, A., Burg, J., Strand, S., Kießlich, R., Huber, S., et al. (2004) · Zeitschrift für Gastroenterologie · doi:10.1055/s-2004-831593 · Cited by 67
Self-citationNo inhibition of IL-27 signaling by soluble gp130
Scheller, J., Schuster, B., Hölscher, C., Yoshimoto, T., & Rose‐John, S. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.11.098 · Cited by 66 · cited 3×
“Interestingly, gp130 is also a receptor subunit of the receptor complexes for IL-11, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), oncostatin M (OSM), cardiotrophin-1 (CT-1), cardiotrophin like cytokine (CLC) and IL-27.”
BackgroundInfluentialSelf-citationSodenkamp, J., Waetzig, G. H., Scheller, J., Seegert, D., Grötzinger, J., Rose‐John, S., Ehlers, S., & Hölscher, C. (2012) · Immunobiology · doi:10.1016/j.imbio.2012.01.015 · Cited by 66 · cited 1×
“whereas treatment with neutralizing TNFα-antibodies resulted in a 10-100 fold increase in mycobacterial colony forming units in the respective organs [75].”
BackgroundSelf-citationZhang, J., Zhang, Y., Owczarek, C. M., Ward, L. D., Moritz, R. L., Simpson, R. J., Yasukawa, K., & Nicola, N. A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.17.10798 · Cited by 63 · cited 2×
“This form of sgp130 called gp130-RAPS only comprises the Ig-like N-terminal domain as well as the cytokine binding domain of gp130 and therefore has a molecular weight of only around 50 kDa [33].”
BackgroundMeads, M. B., & Medveczky, P. G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407382200 · Cited by 62
Finotto, S., Eigenbrod, T., Karwot, R., Boross, I., Doganci, A., Ito, H., Nishimoto, N., Yoshizaki, K., Kishimoto, T., Rose‐John, S., et al. (2007) · International Immunology · doi:10.1093/intimm/dxm037 · Cited by 60 · cited 1×
“Asthma Late-phase murine asthma model after OVA sensitization [67, 102]”
BackgroundSelf-citationgp130 dimerization in the absence of ligand: Preformed cytokine receptor complexes
Tenhumberg, S., Schuster, B., Zhu, L., Kovaleva, M., Scheller, J., Kallen, K., & Rose‐John, S. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.05.173 · Cited by 58 · cited 2×
“The dimerization of gp130 found in the absence of receptor stimulation [57, 58] apparently does not position the transmembrane domains and cytoplasmic domains of gp130 in a way that is sufficient to induce gp130 signaling.”
BackgroundSelf-citationAdam, N., Rabe, B., Suthaus, J., Grötzinger, J., Rose‐John, S., & Scheller, J. (2009) · Journal of Virology · doi:10.1128/jvi.01601-08 · Cited by 57 · cited 1×
“This was confirmed by the structure of vIL-6 bound to the extracellular portion of gp130 [85] and by the definition of the amino acid sequences responsible for the ability of vIL-6 to directly bind to and activate gp130 [86].”
BackgroundSelf-citationHuman herpes virus 8 interleukin‐6 homologue triggers gp130 on neuronal and hematopoietic cells
Hoischen, S. H., Vollmer, P., März, P., Özbek, S., Götze, K. S. S., Peschel, C., Jostock, T., Geib, T., Müllberg, J., Mechtersheimer, S., et al. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.01389.x · Cited by 53 · cited 1×
“Interestingly, it could be shown that vIL-6 directly bound to gp130 without the need of soluble of membrane bound IL-6R and that association with gp130 was sufficient to induce STAT3-dependent proliferation of cells [83, 84].”
BackgroundSelf-citationThe interleukin-6 pathway and atherosclerosis
Boekholdt, S. M., & Stroes, E. S. G. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60361-4 · Cited by 49 · cited 1×
“This effect of this single nucleotide polymorphism was explained with the loss of membrane bound IL-6R from hepatocytes, monocytes, and macrophages and a concomitant loss of IL-6 signaling in these cells [73].”
BackgroundSuthaus, J., Tillmann, A., Lorenzen, I., Bulanova, E., Rose‐John, S., & Scheller, J. (2010) · Molecular Biology of the Cell · doi:10.1091/mbc.e10-03-0240 · Cited by 44 · cited 2×
“To address this question a gp130 cDNA was constructed, in which the entire region coding for the extracellular portion was replaced by DNA sequences coding for the leucine-zipper from the Jun protein [59, 60].”
BackgroundMethodSelf-citationViral Interleukin-6: Structure, pathophysiology and strategies of neutralization
Suthaus, J., Adam, N., Grötzinger, J., Scheller, J., & Rose‐John, S. (2010) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2010.10.016 · Cited by 41 · cited 1×
“Since vIL-6 is the only known cytokine, which can stimulate gp130 without the help of an additional receptor protein, we speculated that vIL-6 was a natural model for IL-6 trans-signaling [89-91].”
BackgroundSelf-citationThe human interleukin‐6 (IL‐6) receptor exists as a preformed dimer in the plasma membrane
Schuster, B., Meinert, W., Rose‐John, S., & Kallen, K. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00154-6 · Cited by 41 · cited 1×
“Interestingly, in a different study it had been observed that also the membrane bound IL-6R on cells was dimeric although the function of this dimerization so far remains unclear [61].”
BackgroundSelf-citationKovaleva, M., Bußmeyer, I., Rabe, B., Grötzinger, J., Sudarman, E., Eichler, J., Conrad, U., Rose‐John, S., & Scheller, J. (2006) · Journal of Virology · doi:10.1128/jvi.00420-06 · Cited by 41
Self-citationViral IL-6 Blocks Neutrophil Infiltration during Acute Inflammation1
Fielding, C., McLoughlin, R., Colmont, C. S., Kovaleva, M., Harris, D., Rose-John, S., Topley, N., & Jones, S. A. (2005) · Journal of Immunology · doi:10.4049/jimmunol.175.6.4024 · Cited by 39 · cited 1×
“Indeed, it could be shown that vIL-6 affects neutrophil infiltration during acute inflammation in a similar way as the IL-6/sIL-6R complex [92].”
BackgroundSelf-citationHuman herpesvirus 8-derived viral IL-6 induces PTX3 expression in Kaposi's sarcoma cells
Klouche, M., Brockmeyer, N. H., Knabbe, C., & Rose‐John, S. (2002) · AIDS · doi:10.1097/00002030-200205240-00001 · Cited by 38 · cited 1×
“Since vIL-6 is the only known cytokine, which can stimulate gp130 without the help of an additional receptor protein, we speculated that vIL-6 was a natural model for IL-6 trans-signaling [89-91].”
BackgroundSelf-citationDiamant, M., Hansen, M., Rieneck, K., Svenson, M., Yasukawa, K., & Bendtzen, K. (1996) · Leukemia research : a Forum for Studies on Leukemia and Normal Hemopoiesis · doi:10.1016/0145-2126(95)00077-1 · Cited by 18 · cited 1×
“The soluble forms of sgp130 were found not to be generated by proteolytic cleavage [35] but rather by translation from alternatively spliced mRNA [36].”
BackgroundDeLeo, F. R. (2007) · Blood · doi:10.1182/blood-2007-06-096677 · Cited by 14
Development of progressive kidney damage and myeloma kidney in interleukin-6 transgenic mice
Fattori, E., Rocca, C. D., Costa, P., et al. (1994) · Blood · doi:10.1182/blood.v83.9.2570.bloodjournal8392570 · Cited by 13 · cited 1×
“The sIL-6R transgenic mice were crossed with mice, which were transgenic for human IL-6 [39].”
BackgroundAtreya, R. N., Finotto, S., Mudter, J., Mullberg, J., Jostock, T., Holtmann, M. H., Kishimoto, T., Galle, P. R., Rose‐John, S., & Neurath, M. F. (2000) · Gastroenterology · doi:10.1016/s0016-5085(00)85593-6 · Cited by 12
Self-citationSoluble cytokine-receptors are present in normal human urine
Novick, D., Engelmann, H., Wallach, D., & Rubinstein, M. (1989) · Cytokine · doi:10.1016/1043-4666(89)91511-1 · Cited by 7
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“This soluble IL-6/IL-6 receptor complex binds to gp130 and therefore can also induce signaling in cell types that do not express membrane bound IL-6 receptors [59].”
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“It has been reported that it has regenerative and anti-inflammatory effects mediated by the conventional signaling process, although it also exerts proinflammatory effects mediated by trans-signaling, as in the case of viral infections [76].”
Metadata
- Authors
- Rose-John, S.
- Venue
- International Journal of Biological Sciences
- Publisher
- Ivyspring International Publisher
- Published
- 2012
- Volume
- 8
- Issue
- 9
- Pages
- 1237-1247
- ISSN
- 1449-2288 (ISSN-L)
- PMC
- PMC3491447
- OpenAlex
- W2100478793
- Cited by
- 1,040
- References
- 110
- Citations by year
- 2026: 87 · 2025: 98 · 2024: 77 · 2023: 73 · 2022: 94 · 2021: 108 · 2020: 107 · 2019: 76 · 2018: 72 · 2017: 65 · 2016: 49 · 2015: 48 · 2014: 54 · 2013: 30 · 2012: 1
- FWCI
- 4.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- International Journal of Biological Sciences (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB654, SFB841, project C1; SFB877, project A1, SFB 877, SFB841 project C1, SFB877, project A1, SFB 841)
- Exzellenzclusters Entzündungsforschung
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- interleukin-6, IL-6 trans-signaling, soluble IL-6 receptor, gp130, IL-6 receptor, pro-inflammatory activity, cytokine signaling, liver regeneration, anti-inflammatory activity, IL-6 inhibition, hepatocytes, leukocytes
- MeSH terms
- Animals, Humans, Mice, Transgenic, Models, Biological, Solubility, Signal Transduction, Interleukin-6, Receptors, Interleukin-6, Cytokine Receptor gp130, Mice
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