Stefan Rose-John

Summary

Affiliation: University of Kiel
Country: Germany

Publications

  1. pmc Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice
    Athena Chalaris
    Institute of Biochemistry, Christian Albrechts University Kiel, D 24098 Kiel, Germany
    J Exp Med 207:1617-24. 2010
  2. doi request reprint ADAM17, shedding, TACE as therapeutic targets
    Stefan Rose-John
    Biochemisches Institut, Christian Albrechts Universitat, Kiel, Germany
    Pharmacol Res 71:19-22. 2013
  3. pmc IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6
    Stefan Rose-John
    Institute of Biochemistry, Christian Albrechts University of Kiel, Kiel, Germany
    Int J Biol Sci 8:1237-47. 2012
  4. pmc A designer hyper interleukin 11 (H11) is a biologically active cytokine
    Hanna Dams-Kozlowska
    Department of Cancer Diagnostics and Immunology, Greater Poland Cancer Centre, 15 Garbary St, 61 866 Poznan, Poland
    BMC Biotechnol 12:8. 2012
  5. ncbi request reprint GP130 stimulation and the maintenance of stem cells
    Stefan Rose-John
    Institut fur Biochemie, Christian Albrechts Universitat zu Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    Trends Biotechnol 20:417-9. 2002
  6. ncbi request reprint Interleukin-6 biology is coordinated by membrane bound and soluble receptors
    Stefan Rose-John
    Department of Biochemistry, Christian Albrechts Universitat zu Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    Acta Biochim Pol 50:603-11. 2003
  7. ncbi request reprint Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer
    Stefan Rose-John
    Biochemisches Institut, Christian Albrechts Universitat zu Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    J Leukoc Biol 80:227-36. 2006
  8. ncbi request reprint CDP-870. Celltech/Pfizer
    Stefan Rose-John
    Department of Biochemistry, Christian Albrechts Universitat zu Kiel, 40 Olshausenstrasse, D 24098 Kiel, Germany
    Curr Opin Investig Drugs 4:588-92. 2003
  9. ncbi request reprint Interleukin-6 trans-signaling and colonic cancer associated with inflammatory bowel disease
    Stefan Rose-John
    Department of Biochemistry, Christian Albrechts University, D 24098 Kiel, Germany
    Curr Pharm Des 15:2095-103. 2009
  10. ncbi request reprint The IL-6/sIL-6R complex as a novel target for therapeutic approaches
    Stefan Rose-John
    Biochemisches Institut, Christian Albrechts Universitat zu Kiel, Kiel, Germany
    Expert Opin Ther Targets 11:613-24. 2007

Collaborators

Detail Information

Publications106 found, 100 shown here

  1. pmc Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice
    Athena Chalaris
    Institute of Biochemistry, Christian Albrechts University Kiel, D 24098 Kiel, Germany
    J Exp Med 207:1617-24. 2010
    ..Thus, our mouse model will help investigate ADAM17 as a potential drug target...
  2. doi request reprint ADAM17, shedding, TACE as therapeutic targets
    Stefan Rose-John
    Biochemisches Institut, Christian Albrechts Universitat, Kiel, Germany
    Pharmacol Res 71:19-22. 2013
    ..Here I summarize data on the physiologic role of ADAM17 and the feasibility of specific blockade of this enzyme...
  3. pmc IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6
    Stefan Rose-John
    Institute of Biochemistry, Christian Albrechts University of Kiel, Kiel, Germany
    Int J Biol Sci 8:1237-47. 2012
    ..Furthermore, the detailed knowledge of IL-6 biology has important consequences for therapeutic strategies aimed at the blockade of the cytokine IL-6...
  4. pmc A designer hyper interleukin 11 (H11) is a biologically active cytokine
    Hanna Dams-Kozlowska
    Department of Cancer Diagnostics and Immunology, Greater Poland Cancer Centre, 15 Garbary St, 61 866 Poznan, Poland
    BMC Biotechnol 12:8. 2012
    ..Such a construct has two major advantages: (i) its components are as close as possible to the natural forms of both proteins and (ii) it lacks an artificial linker what should avoid induction of antibody production...
  5. ncbi request reprint GP130 stimulation and the maintenance of stem cells
    Stefan Rose-John
    Institut fur Biochemie, Christian Albrechts Universitat zu Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    Trends Biotechnol 20:417-9. 2002
    ..This article summarizes what is known about, and the problems associated with, the cultivation of stem cells and suggests experimental strategies that might help to overcome these difficulties...
  6. ncbi request reprint Interleukin-6 biology is coordinated by membrane bound and soluble receptors
    Stefan Rose-John
    Department of Biochemistry, Christian Albrechts Universitat zu Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    Acta Biochim Pol 50:603-11. 2003
    ..The mechanism by which the IL-6/ soluble IL-6R complex regulates the inflammatory state is discussed...
  7. ncbi request reprint Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer
    Stefan Rose-John
    Biochemisches Institut, Christian Albrechts Universitat zu Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    J Leukoc Biol 80:227-36. 2006
    ..The pathophysiological mechanisms by which the IL-6/sIL-6R complex regulates the inflammatory state are discussed...
  8. ncbi request reprint CDP-870. Celltech/Pfizer
    Stefan Rose-John
    Department of Biochemistry, Christian Albrechts Universitat zu Kiel, 40 Olshausenstrasse, D 24098 Kiel, Germany
    Curr Opin Investig Drugs 4:588-92. 2003
    ..In October 2002, Pharmacia initiated phase III trials for RA and at this time Celltech anticipated initiating phase III trials for CD in mid-2003...
  9. ncbi request reprint Interleukin-6 trans-signaling and colonic cancer associated with inflammatory bowel disease
    Stefan Rose-John
    Department of Biochemistry, Christian Albrechts University, D 24098 Kiel, Germany
    Curr Pharm Des 15:2095-103. 2009
    ....
  10. ncbi request reprint The IL-6/sIL-6R complex as a novel target for therapeutic approaches
    Stefan Rose-John
    Biochemisches Institut, Christian Albrechts Universitat zu Kiel, Kiel, Germany
    Expert Opin Ther Targets 11:613-24. 2007
    ..An optimised variant of the recently described fusion protein sgp30Fc is now heading towards its clinical evaluation...
  11. ncbi request reprint Cellular cholesterol depletion triggers shedding of the human interleukin-6 receptor by ADAM10 and ADAM17 (TACE)
    Vance Matthews
    Biochemisches Institut, Christian Albrechts Universitat zu Kiel, Germany
    J Biol Chem 278:38829-39. 2003
    ..For decades, high cholesterol levels have been considered harmful. This study indicates that low cholesterol levels may play a role in shedding of the membrane-bound IL-6R and thereby in the immunopathogenesis of human diseases...
  12. ncbi request reprint The upper cytokine-binding module and the Ig-like domain of the leukaemia inhibitory factor (LIF) receptor are sufficient for a functional LIF receptor complex
    Dorthe Aasland
    Biochemisches Institut, Christian Albrechts Universitat Kiel, Ohlshausenstr 40, Kiel, D 24098, Germany
    J Mol Biol 315:637-46. 2002
    ..An additional contact is postulated between the Ig-like domain of gp130 and the NH(2)-terminal CBM of the LIFR...
  13. ncbi request reprint The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion
    Christian Hundhausen
    Institute for Biochemistry, Christian Albrechts University, Kiel, Germany
    Blood 102:1186-95. 2003
    ..Our data demonstrate that ADAM10 is involved in the constitutive cleavage of CX3CL1 and thereby may regulate the recruitment of monocytic cells to CX3CL1-expressing cell layers...
  14. ncbi request reprint Signaling of human ciliary neurotrophic factor (CNTF) revisited. The interleukin-6 receptor can serve as an alpha-receptor for CTNF
    Björn Schuster
    Biochemisches Institut, Christian Albrechts Universitat zu Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    J Biol Chem 278:9528-35. 2003
    ..Engineering a CNTFR-specific human CNTF variant may therefore be a prerequisite to improving the safety profile of CNTF...
  15. doi request reprint Soluble T cell immunoglobulin and mucin domain (TIM)-1 and -4 generated by A Disintegrin And Metalloprotease (ADAM)-10 and -17 bind to phosphatidylserine
    Olga Schweigert
    Institute of Biochemistry, Medical Faculty, Christian Albrechts University, Kiel, Germany
    Biochim Biophys Acta 1843:275-87. 2014
    ..In summary, we describe TIM-1 and TIM-4 as novel targets for ADAM10- and ADAM17-mediated ectodomain shedding. ..
  16. doi request reprint Structure-guided optimization of the interleukin-6 trans-signaling antagonist sgp130
    Stephanie Tenhumberg
    Institute of Biochemistry, Christian Albrechts University Kiel, D 24098 Kiel, Germany
    J Biol Chem 283:27200-7. 2008
    ..Finally, we demonstrate the species specificity of these mutations in the optimal triple mutein (T102Y/Q113F/N114L) both in vitro and in a mouse model of acute inflammation...
  17. doi request reprint T-cell immunoglobulin and mucin domain 2 (TIM-2) is a target of ADAM10-mediated ectodomain shedding
    Christin Dewitz
    Institute of Biochemistry, Medical Faculty, Christian Albrechts University, Kiel, Germany
    FEBS J 281:157-74. 2014
    ..Shed and soluble TIM-2 interacted with H-ferritin. In summary, we describe TIM-2 as a novel target for ADAM10-mediated ectodomain shedding, and reveal the involvement of ADAM proteases in cellular iron homeostasis. ..
  18. ncbi request reprint Apoptosis is a natural stimulus of IL6R shedding and contributes to the proinflammatory trans-signaling function of neutrophils
    Athena Chalaris
    Department of Biochemistry, Christian Albrechts University, Kiel, Germany
    Blood 110:1748-55. 2007
    ....
  19. ncbi request reprint Transgenic blockade of interleukin 6 transsignaling abrogates inflammation
    Björn Rabe
    Department of Biochemistry, Christian Albrechts University, Kiel, Germany
    Blood 111:1021-8. 2008
    ..In these mice, inflammatory processes are blocked as in IL6(-/-) mice, strongly arguing for a major role of the soluble IL6R during inflammation in vivo...
  20. pmc Unraveling viral interleukin-6 binding to gp130 and activation of STAT-signaling pathways independently of the interleukin-6 receptor
    Nina Adam
    Institute of Biochemistry, Christian Albrechts University of Kiel, Olshausenstrasse 40, D 24098 Kiel, Germany
    J Virol 83:5117-26. 2009
    ..These data indicate a novel activation mechanism of human IL-6 by the IL-6R that will be important for the construction of novel hyperactive cytokine variants...
  21. doi request reprint Role of IL-6 trans-signaling in CCl₄induced liver damage
    Jessica Gewiese-Rabsch
    Institute of Biochemistry, Christian Albrechts University of Kiel, Kiel, Germany
    Biochim Biophys Acta 1802:1054-61. 2010
    ..We conclude that IL-6 trans-signaling via the soluble IL-6R is important for the physiologic response of the liver to CCl₄ induced chemical damage...
  22. ncbi request reprint The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10
    Soeren Abel
    Institute for Biochemistry, Christian Albrechts University, Kiel, Germany
    J Immunol 172:6362-72. 2004
    ..Hence, during inflammation in the vasculature, ADAM10 may act as a CXCL16 sheddase and thereby finely control the expression and function of CXCL16 in the inflamed tissue...
  23. ncbi request reprint Development of a monoclonal antibody-based enzyme-linked immunoabsorbent assay for the binding of gp130 to the IL-6/IL-6R complex and its competitive inhibition
    Jürgen Scheller
    Institut fur Biochemie, Christian Albrechts Universitat zu Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    J Immunol Methods 291:93-100. 2004
    ..The assay can be used for high-throughput screening of peptide and chemical compound libraries for the identification of new agonists and antagonists of the binding between gp130 and IL-6/sIL-6R...
  24. doi request reprint ADAM17-mediated shedding of the IL6R induces cleavage of the membrane stub by gamma-secretase
    Athena Chalaris
    Institute of Biochemistry, Christian Albrechts University of Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    Biochim Biophys Acta 1803:234-45. 2010
    ..No GFP-fluorescence of a gamma-secretase-cleaved IL6R-GFP fusion protein was observed in the nucleus. We therefore hypothesize that a potential IL6R intracellular domain fragment is not involved in nuclear signaling but rapidly degraded...
  25. ncbi request reprint No inhibition of IL-27 signaling by soluble gp130
    Jürgen Scheller
    Institut fur Biochemie, Christian Albrechts Universitat zu Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    Biochem Biophys Res Commun 326:724-8. 2005
    ..Here we show that sgp130-Fc does not interfere with IL-27 signaling. We therefore conclude that IL-27 does not bind with high affinity to gp130...
  26. ncbi request reprint gp130 dimerization in the absence of ligand: preformed cytokine receptor complexes
    Stephanie Tenhumberg
    Department of Biochemistry, Christian Albrechts University Kiel, Olshausenstrasse 40, D 24098 Kiel, Germany
    Biochem Biophys Res Commun 346:649-57. 2006
    ..The present study clearly demonstrates the existence of preformed but inactive gp130/LIF-R hetero- and gp130/gp130 homo-dimers. The addition of ligand enhanced the respective dimer formation and was required for signal transduction...
  27. doi request reprint Interleukin-6 trans-signaling regulates glycogen consumption after D-galactosamine-induced liver damage
    Claudia Drucker
    Institute of Biochemistry, Christian Albrechts University of Kiel, Olshausenstrasse 40, Kiel, Germany
    J Interferon Cytokine Res 29:711-8. 2009
    ..Taken together our results show that upon liver damage, activation of the gp130 pathway depends on the sIL-6R...
  28. doi request reprint G protein-coupled receptor 43 is essential for neutrophil recruitment during intestinal inflammation
    Christian Sina
    Institute of Clinical Molecular Biology, University Hospital Schleswig Holstein, Kiel, Germany
    J Immunol 183:7514-22. 2009
    ....
  29. pmc Abrogation of viral interleukin-6 (vIL-6)-induced signaling by intracellular retention and neutralization of vIL-6 with an anti-vIL-6 single-chain antibody selected by phage display
    Marina Kovaleva
    Department of Biochemistry, Christian Albrechts Universitat, Kiel, Germany
    J Virol 80:8510-20. 2006
    ..We conclude that the activity of the intracellularly retained vIL-6 protein is neutralized by MAV-KDEL. Our results might represent a novel therapeutic strategy to neutralize virally encoded growth factors or oncogenes...
  30. ncbi request reprint The human interleukin-6 (IL-6) receptor exists as a preformed dimer in the plasma membrane
    Björn Schuster
    Biochemisches Institut, Christian Albrechts Universitat zu Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    FEBS Lett 538:113-6. 2003
    ..When lysates of COS-7 cells expressing only one of the IL-6R variants are mixed, spontaneous dimerization occurs. Thus, the IL-6R dimer observed in the crystal structure represents a physiologically occurring phenomenon...
  31. ncbi request reprint Direct determination of the interleukin-6 binding epitope of the interleukin-6 receptor by NMR spectroscopy
    Andreas Schwantner
    Biochemisches Institut, Christian Albrechts Universitat Kiel, Olshausenstrasse 40, 24118 Kiel, Germany
    J Biol Chem 279:571-6. 2004
    ....
  32. doi request reprint A novel bispecific single-chain antibody for ADAM17 and CD3 induces T-cell-mediated lysis of prostate cancer cells
    Kosuke Yamamoto
    Institute of Biochemistry, Christian Albrechts University of Kiel, Kiel, Germany
    Biochem J 445:135-44. 2012
    ..In the presence of primary human peripheral blood mononuclear cells or human T-cells the addition of A300E-BiTE led to ADAM17-specific killing of prostate tumour cells indicating a novel strategy for the treatment of cancer...
  33. pmc Forced homo- and heterodimerization of all gp130-type receptor complexes leads to constitutive ligand-independent signaling and cytokine-independent growth
    Jan Suthaus
    Department of Biochemistry, Christian Albrechts Universitat, D 24098 Kiel, Germany
    Mol Biol Cell 21:2797-807. 2010
    ....
  34. doi request reprint Essential role of neutrophil mobilization in concanavalin A-induced hepatitis is based on classic IL-6 signaling but not on IL-6 trans-signaling
    Sven Malchow
    Institute of Biochemistry, Christian Albrechts University of Kiel, Kiel, Germany
    Biochim Biophys Acta 1812:290-301. 2011
    ....
  35. pmc Species specificity of ADAM10 and ADAM17 proteins in interleukin-6 (IL-6) trans-signaling and novel role of ADAM10 in inducible IL-6 receptor shedding
    Christoph Garbers
    Institute of Biochemistry, Christian Albrechts University, Olshausenstrasse 40, Kiel, Germany
    J Biol Chem 286:14804-11. 2011
    ....
  36. ncbi request reprint Impaired hippocampus-dependent and -independent learning in IL-6 deficient mice
    Paul Christian Baier
    Dept of Psychiatry and Psychotherapy, Christian Albrechts University Kiel, 24105 Kiel, Germany
    Behav Brain Res 200:192-6. 2009
    ..However, it remains unclear if impairments of memory are a specific result of disturbed IL-6 signalling, or rather an epiphenomenon associated with reduced exploratory behaviour and stress resistance...
  37. ncbi request reprint Analysis of the leukemia inhibitory factor receptor functional domains by chimeric receptors and cytokines
    Dorthe Aasland
    Biochemisches Institut, Christian Albrechts Universitat Kiel, Germany
    Biochemistry 42:5244-52. 2003
    ..e., a functional receptor complex of IL-6 type cytokines cannot be assembled solely via site I and II as in the growth hormone receptor complex...
  38. ncbi request reprint Soluble tumor necrosis factor (TNF) receptor-1 induces apoptosis via reverse TNF signaling and autocrine transforming growth factor-beta1
    Georg H Waetzig
    Institute of Clinical Molecular Biology, Schleswig Holstein University Medical Center, Kiel, Germany
    FASEB J 19:91-3. 2005
    ..This novel mechanism has implications for understanding the physiological role of sTNFR1 and for TNF-alpha-blocking therapies of autoimmune diseases...
  39. ncbi request reprint The solution structure of the membrane-proximal cytokine receptor domain of the human interleukin-6 receptor
    Oliver Hecht
    Biochemisches Institut der Christian Albrechts Universität Kiel, Olshausenstr 40, D 24118 Kiel, Germany
    Biol Chem 387:1255-9. 2006
    ..Here, we present the solution structure of the IL-6R-D3 domain solved by multidimensional heteronuclear NMR spectroscopy...
  40. ncbi request reprint gp130 activation is regulated by D2-D3 interdomain connectivity
    Antje Schütt
    Christian Albrechts Universitat zu Kiel, Institute of Biochemistry, Rudolf Höber Strasse 1, 24118 Kiel, Germany
    Biochem J 450:487-96. 2013
    ..Taken together we present novel insights into the molecular basis of the activation of a cytokine receptor signalling subunit...
  41. doi request reprint Interleukin-6 trans-signaling and colonic cancer associated with inflammatory bowel disease
    Athena Chalaris
    Institute of Biochemistry, Christian Albrechts University, Kiel, Germany
    Dig Dis 30:492-9. 2012
    ..These results are important for strategies to inhibit IL-6 signaling in autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and inflammation-associated colorectal cancer...
  42. doi request reprint The membrane-proximal domain of A Disintegrin and Metalloprotease 17 (ADAM17) is responsible for recognition of the interleukin-6 receptor and interleukin-1 receptor II
    Inken Lorenzen
    Institute of Biochemistry, Christian Albrechts University, Kiel, Germany
    FEBS Lett 586:1093-100. 2012
    ..In the extracellular part solely the membrane-proximal domain of ADAM17 is mandatory for recognition of the two type-I transmembrane proteins, but not for the interaction with the type-II transmembrane molecule TNF-α...
  43. ncbi request reprint Cytokines are a therapeutic target for the prevention of inflammation-induced cancers
    Stefan Rose-John
    Biochemisches Institut, Christian Albrechts Universitat zu Kiel, Germany
    Recent Results Cancer Res 174:57-66. 2007
    ..These designer cytokines have been shown to be extremely useful in therapeutic applications such as blockade of chronic inflammation and cancer...
  44. doi request reprint Impact of interleukin-6 classic- and trans-signaling on liver damage and regeneration
    Claudia Drucker
    Institute of Biochemistry, Christian Albrechts University of Kiel, Kiel, Germany
    J Autoimmun 34:29-37. 2010
    ..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...
  45. pmc Polo-like kinase 2, a novel ADAM17 signaling component, regulates tumor necrosis factor α ectodomain shedding
    Jeanette Schwarz
    From the Institute of Biochemistry, Christian Albrechts Universitat zu Kiel, 24118 Kiel, Germany
    J Biol Chem 289:3080-93. 2014
    ..Our findings suggest a new role for PLK2 in the regulation of inflammatory diseases by modulating ADAM17 activity. ..
  46. doi request reprint Effects of blockade of peripheral interleukin-6 trans-signaling on hippocampus-dependent and independent memory in mice
    Olga Braun
    Department of Biochemistry, Christian Albrechts University Kiel, Kiel, Germany
    J Interferon Cytokine Res 33:254-60. 2013
    ..These results bear important consequences for the therapeutic blockade of IL-6 activity in autoimmune diseases...
  47. pmc Functional expression of a biologically active fragment of soluble gp130 as an ELP-fusion protein in transgenic plants: purification via inverse transition cycling
    Meng Lin
    Biochemisches Institut, Christian Albrechts Universitat zu Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    Biochem J 398:577-83. 2006
    ..Consequently, the present study validates the potential application of molecular farming in transgenic tobacco plants as a strategy for the expression and purification of therapeutically advantageous biologics such as sgp130...
  48. pmc Forced dimerization of gp130 leads to constitutive STAT3 activation, cytokine-independent growth, and blockade of differentiation of embryonic stem cells
    Christiane Stuhlmann-Laeisz
    Department of Biochemistry, Christian Albrechts Universitat, D 24098 Kiel, Germany
    Mol Biol Cell 17:2986-95. 2006
    ..Thus, L-gp130 can be used in vitro and in vivo to mimic constitutive and ligand-independent activation of gp130 and STAT3, the latter of which is frequently observed in neoplastic diseases...
  49. doi request reprint mTNF reverse signalling induced by TNFα antagonists involves a GDF-1 dependent pathway: implications for Crohn's disease
    Stefanie Derer
    Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany
    Gut 62:376-86. 2013
    ..The aim of this study was to analyse transcriptomal responses of reverse signalling induced by the TNFα binding agents infliximab (IFX) and CZP in myelomonocytic cells...
  50. ncbi request reprint Interleukin 27 induces differentiation of neural C6-precursor cells into astrocytes
    Manuel Koch
    Biochemisches Institut, Christian Albrechts Universitat, Kiel, Olshausenstrasse 40, D 24098 Kiel, Germany
    Biochem Biophys Res Commun 364:483-7. 2007
    ..These data could be confirmed by GFAP-immunostaining of stimulated cells. Taken together, IL27 and vIL6 can be considered as new astrocyte-inducing cytokines of the brain...
  51. doi request reprint The soluble Interleukin 6 receptor: generation and role in inflammation and cancer
    Athena Chalaris
    Institute of Biochemistry, Christian Albrechts University, Olshausenstraße 40, Kiel, Germany
    Eur J Cell Biol 90:484-94. 2011
    ....
  52. doi request reprint Transglutaminase-catalyzed covalent multimerization of Camelidae anti-human TNF single domain antibodies improves neutralizing activity
    Ingo Plagmann
    Department of Biochemistry, Christian Albrechts Universitat zu Kiel, Olshausenstrasse 40, D 24098 Kiel, Germany
    J Biotechnol 142:170-8. 2009
    ..We hypothesize that improved inhibition by dimeric and multimeric single chain hTNF-V(H)H proteins is caused by avidity effects...
  53. ncbi request reprint Interleukin-6 and its receptor: from bench to bedside
    Jürgen Scheller
    Institut fur Biochemie, Christian Albrechts Universitat zu Kiel, Olshausenstr 40, 24098 Kiel, Germany
    Med Microbiol Immunol 195:173-83. 2006
    ..These designer cytokines have been shown to be extremely useful to in therapeutic applications ranging from the long-term culture of stem cells and enhancing liver regeneration up to the blockade of chronic inflammation and cancer...
  54. ncbi request reprint Designing cytokine variants by phage-display
    Heidi Schooltink
    Institut fur Biochemie, Christian Albrechts Universitat zu Kiel, D 24098 Kiel, Germany
    Comb Chem High Throughput Screen 8:173-9. 2005
    ..Surprisingly, such mimetic peptides do not show any sequence similarity to the parental cytokines. Such peptide mimetics can be used as lead structures for the generation of non-peptidic chemical compounds with cytokine activity...
  55. pmc HHV-8-encoded viral IL-6 collaborates with mouse IL-6 in the development of multicentric Castleman disease in mice
    Jan Suthaus
    Institute of Biochemistry, Christian Albrechts University, Kiel, Germany
    Blood 119:5173-81. 2012
    ..Our results in mice suggest that human IL-6 plays an important role in the pathogenesis of HHV-8-associated MCD...
  56. doi request reprint Elastin-like polypeptides revolutionize recombinant protein expression and their biomedical application
    Doreen M Floss
    Institute of Biochemistry, Christian Albrechts University, Olshausenstrasse 40, D 24098 Kiel, Germany
    Trends Biotechnol 28:37-45. 2010
    ..Here, we discuss recent developments in ELP technology and the substantial potential of ELPs for the deployment of transgenic plants as bioreactors to synthesize both biopharmaceuticals and industrial proteins...
  57. doi request reprint The structure of the unliganded extracellular domain of the interleukin-6 signal transducer gp130 in solution
    Inken Lorenzen
    Institute of Biochemistry, Christian Albrechts University Kiel, Olshausenstr 40, 24098 Kiel, Germany
    Eur J Cell Biol 90:515-20. 2011
    ..Functional implications of these findings are discussed...
  58. pmc L1 is sequentially processed by two differently activated metalloproteases and presenilin/gamma-secretase and regulates neural cell adhesion, cell migration, and neurite outgrowth
    Thorsten Maretzky
    Biochemical Institute, Christian Albrechts University Kiel, Germany
    Mol Cell Biol 25:9040-53. 2005
    ..Thus, our data identify ADAM10 and ADAM17 as differentially regulated L1 membrane sheddases, both critically affecting the physiological functions of this adhesion protein...
  59. doi request reprint Short-term TNFα shedding is independent of cytoplasmic phosphorylation or furin cleavage of ADAM17
    Jeanette Schwarz
    Institute of Biochemistry, Christian Albrechts University Kiel, 24098 Kiel, Germany
    Biochim Biophys Acta 1833:3355-67. 2013
    ..These results have general implications on understanding the activation mechanism controlling the activity of ADAM17. ..
  60. ncbi request reprint Cytokines as therapeutic drugs
    Heidi Schooltink
    Department of Biochemistry, Christian Albrechts Universitat Kiel, D 24098 Kiel, Germany
    J Interferon Cytokine Res 22:505-16. 2002
    ..Furthermore, cytokines may be good candidates as cancer therapeutics, especially to support the restoration of blood cell populations after chemotherapy or radiation...
  61. doi request reprint Oncogenic deletion mutants of gp130 signal from intracellular compartments
    Dirk Schmidt-Arras
    Christian Albrechts University, Institute of Biochemistry, 24118 Kiel, Germany
    J Cell Sci 127:341-53. 2014
    ..Therefore, aberrant signalling from intracellular compartments might explain the tumorigenic potential of naturally occurring somatic mutations of gp130. ..
  62. doi request reprint ADAM17-overexpressing breast cancer cells selectively targeted by antibody-toxin conjugates
    Ahmad Trad
    Institute of Biochemistry, Christian Albrechts University of Kiel, Olshausenstr 40, 24098, Kiel, Germany
    Cancer Immunol Immunother 62:411-21. 2013
    ..These data suggest that the use of anti-ADAM17 monoclonal antibodies as a carrier might be a promising new strategy for selective anti-cancer drug delivery...
  63. doi request reprint Viral Interleukin-6: Structure, pathophysiology and strategies of neutralization
    Jan Suthaus
    Institute of Biochemistry, Christian Albrechts University of Kiel, Kiel, Germany
    Eur J Cell Biol 90:495-504. 2011
    ..Furthermore, mechanisms of activation of gp130 by hIL-6, vIL-6, and by forced dimerization will be discussed...
  64. ncbi request reprint Altered pulmonary interleukin-6 signaling in preterm infants developing bronchopulmonary dysplasia
    Philipp von Bismarck
    Department of General Pediatrics, Universitatsklinikum Schleswig Holstein, Kiel, Germany
    Exp Lung Res 34:694-706. 2008
    ..The authors conclude that altered interleukin-6 signaling via the soluble receptors sIL-6R and sgp130 may play an important role in pulmonary inflammation of preterm infants...
  65. pmc The substrate degradome of meprin metalloproteases reveals an unexpected proteolytic link between meprin β and ADAM10
    Tamara Jefferson
    Institute of Biochemistry, Christian Albrechts University, 24118, Kiel, Germany
    Cell Mol Life Sci 70:309-33. 2013
    ..Our finding of cystatin C, elafin and fetuin-A as substrates and natural inhibitors for meprins reveal new mechanisms in the regulation of protease activity important for understanding pathophysiological processes...
  66. doi request reprint Hitting a complex target: an update on interleukin-6 trans-signalling
    Georg H Waetzig
    Christian Albrechts University Kiel, Institute of Biochemistry, Kiel, Germany
    Expert Opin Ther Targets 16:225-36. 2012
    ..By contrast, the fusion protein sgp130Fc selectively targets IL-6/sIL-6R trans-signalling by utilising the soluble gp130 receptor as the natural inhibitor of trans-signalling...
  67. doi request reprint IL-6-trans-signalling increases rapid-eye-movement sleep in rats
    Ulrike May
    Biochemisches Institut, Christian Albrechts Universitat zu Kiel, Kiel, Germany
    Eur J Pharmacol 613:141-5. 2009
    ..Our data define a new role of IL-6-trans-signalling in sleep regulation...
  68. pmc Accurate variant detection across non-amplified and whole genome amplified DNA using targeted next generation sequencing
    Abdou ElSharawy
    Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany
    BMC Genomics 13:500. 2012
    ..Three of these samples were also preamplified by WGA and evaluated. We tested sample pooling or multiplexing strategies at different stages of the tested targeted NGS (T-NGS) workflow...
  69. ncbi request reprint IL-6 trans-signaling: the heat is on
    Stefan Rose-John
    Department of Biochemistry, Christian Albrechts Universitat zu Kiel, Olshausenstrasse 40, D 24098, Kiel, Germany
    Immunity 20:2-4. 2004
    ..This L-selectin activation during heat responses was dependent on IL-6 trans-signaling via the soluble IL-6R...
  70. ncbi request reprint The interleukin-6 cytokine system regulates epidermal permeability barrier homeostasis
    Xu Ping Wang
    Department of Dermatology, University of Kiel, Germany
    J Invest Dermatol 123:124-31. 2004
    ..Our results indicate that the IL-6 cytokine system, particularly transsignalling via the soluble IL-6R, is critically involved in barrier repair after skin injury...
  71. pmc The IL-6-gp130-STAT3 pathway in hepatocytes triggers liver protection in T cell-mediated liver injury
    Christian Klein
    Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
    J Clin Invest 115:860-9. 2005
    ..Additionally, we identified the IL-6-gp130-STAT3-dependent proteins KC and SAA2 as new candidates for therapeutic targets in liver diseases...
  72. ncbi request reprint 1H, 15N and 13C backbone assignment of the carboxyl terminal domain of the cytokine binding module of the interleukin-6 receptor
    Andreas Schwantner
    J Biomol NMR 29:407-8. 2004
  73. pmc Interplay between IFN-gamma and IL-6 signaling governs neutrophil trafficking and apoptosis during acute inflammation
    Rachel M McLoughlin
    Institute of Nephrology, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, United Kingdom
    J Clin Invest 112:598-607. 2003
    ..These data emphasize a pivotal role for IFN-gamma in regulating innate immunity through control of both the recruitment and clearance phases of PMN trafficking...
  74. ncbi request reprint Ligand/receptor signaling threshold (LIST) model accounts for gp130-mediated embryonic stem cell self-renewal responses to LIF and HIL-6
    Sowmya Viswanathan
    Institute of Biomaterials and Biomedical Engineering, Roseburgh Building, University of Toronto, 4 Taddle Creek Road, Toronto, Ontario, M5S 3G9, Canada
    Stem Cells 20:119-38. 2002
    ..Insights from these results may be more generally applicable to tissue-specific stem cells and could aid in the development of stem cell-based technologies...
  75. ncbi request reprint Soluble IL-6 receptor governs IL-6 activity in experimental arthritis: blockade of arthritis severity by soluble glycoprotein 130
    Mari A Nowell
    Cardiff School of Biosciences, Cardiff University, Cardiff, Wales, United Kingdom
    J Immunol 171:3202-9. 2003
    ..Specific blockade of soluble IL-6R signaling in wild-type mice using soluble gp130 ameliorated disease. Consequently, soluble IL-6R-mediated signaling represents a promising therapeutic target for the treatment of rheumatoid arthritis...
  76. ncbi request reprint Differential response of neuronal cells to a fusion protein of ciliary neurotrophic factor/soluble CNTF-receptor and leukemia inhibitory factor
    Pia März
    Department of Physiology, University of Basel, Switzerland
    Eur J Biochem 269:3023-31. 2002
    ..The therapeutic potential of Hyper-CNTF as a superagonistic neurotrophin is discussed...
  77. ncbi request reprint Human herpesvirus 8-derived viral IL-6 induces PTX3 expression in Kaposi's sarcoma cells
    Mariam Klouche
    Institute of Clinical Pathology, Department of Laboratory Medicine, Robert Bosch Hospital and Robert Bosch Society for Medical Research, Stuttgart, Germany
    AIDS 16:F9-18. 2002
    ..To analyse if human herpesvirus 8 (HHV8)-derived viral interleukin-6 (vIL-6) has the capacity to activate Kaposi's sarcoma (KS) cells to elicit a local acute-phase response...
  78. ncbi request reprint Towards determining the differentiation program of antigen-presenting dendritic cells by transcriptional profiling
    Xin Sheng Ju
    Max Delbruck Center for Molecular Medicine, MDC, Berlin, Germany
    Eur J Cell Biol 82:75-86. 2003
    ..In contrast, expression of STAT factors increased during DC differentiation and their expression was virtually unaffected by TNFalpha...
  79. ncbi request reprint The role of soluble receptors in cytokine biology: the agonistic properties of the sIL-6R/IL-6 complex
    Simon A Jones
    Molecular Cell Biology Research Group, Cardiff School of Biosciences, Biomedical Sciences Building, Cardiff University, Wales, UK
    Biochim Biophys Acta 1592:251-63. 2002
    ..This review provides an overview of the activities of soluble cytokine receptors, but primarily concentrates on those that possess agonistic properties...
  80. ncbi request reprint The effect of gp130 stimulation on glutamate-induced excitotoxicity in primary hippocampal neurons
    Yi Sun
    College of Life Sciences, Zhejiang University, Hangzhou 310027, PR China
    Biochem Biophys Res Commun 295:532-9. 2002
    ..These data indicate that interleukin-6 receptor expression is very low on hippocampal neurons and that gp130 stimulation can be used to rescue hippocampal neurons from excitotoxicity...
  81. ncbi request reprint Multilevel regulation of IL-6R by IL-6-sIL-6R fusion protein according to the primitiveness of peripheral blood-derived CD133+ cells
    David Campard
    Laboratoire Micro Environnement et le Renouvellement Cellulaire Intégré, Faculte de Medecine, Pharmacie de Rouen, France
    Stem Cells 24:1302-14. 2006
    ..In conclusion, expression and production of IL-6R are tightly regulated and stage specific. We assume that sIL-6R produced by shedding should be involved in autocrine and paracrine loops in the HSC microenvironment...
  82. ncbi request reprint Natural soluble interleukin-15Ralpha is generated by cleavage that involves the tumor necrosis factor-alpha-converting enzyme (TACE/ADAM17)
    Vadim Budagian
    Center for Cancer Drug Discovery and Development, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 279:40368-75. 2004
    ..The existence of natural sIL-15Ralpha offers novel insights into the complex biology of IL-15 and envisages a new level for therapeutic intervention...
  83. ncbi request reprint Interleukin-6 trans-signaling in inflammatory bowel disease
    Keiichi Mitsuyama
    Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Asahi machi 67, Kurume 830 0011, Japan
    Cytokine Growth Factor Rev 17:451-61. 2006
    ..These studies suggest that IL-6 trans-signaling may play a role in the development of IBD; they therefore imply the possibility of a selective therapeutic strategy to target this signaling...
  84. ncbi request reprint Local blockade of IL-6R signaling induces lung CD4+ T cell apoptosis in a murine model of asthma via regulatory T cells
    Susetta Finotto
    Laboratory of Cellular and Molecular Immunology of the Lung, First Medical Clinic, University of Mainz, Germany
    Int Immunol 19:685-93. 2007
    ..Local targeting of IL-6R signaling could be a novel approach for inducing Th2 T cell death in allergic airways via regulatory T cells...
  85. pmc Classic interleukin-6 receptor signaling and interleukin-6 trans-signaling differentially control angiotensin II-dependent hypertension, cardiac signal transducer and activator of transcription-3 activation, and vascular hypertrophy in vivo
    Barbara Coles
    Dept of Medical Biochemistry and Immunology, Heath Park, Cardiff, UK
    Am J Pathol 171:315-25. 2007
    ..Inhibition of IL-6 signaling is suggested as a potential therapy for hypertension and cardiac hypertrophy...
  86. ncbi request reprint Cutting edge: trans-signaling via the soluble IL-6R abrogates the induction of FoxP3 in naive CD4+CD25 T cells
    Sabine Dominitzki
    Laboratory of Immunology, Medical Clinic I, University of Mainz, Mainz, Germany
    J Immunol 179:2041-5. 2007
    ....
  87. ncbi request reprint Conservation of IL-6 trans-signaling mechanisms controlling L-selectin adhesion by fever-range thermal stress
    Michelle M Appenheimer
    Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263 0001, USA
    Eur J Immunol 37:2856-67. 2007
    ....
  88. ncbi request reprint IL-6 transsignaling: the in vivo consequences
    Simon A Jones
    Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, Wales, UK
    J Interferon Cytokine Res 25:241-53. 2005
    ..The mechanism by which the IL-6/sIL-6R complex regulates the inflammatory or neoplastic state is discussed...
  89. ncbi request reprint IL6/sIL6R complex contributes to emergency granulopoietic responses in G-CSF- and GM-CSF-deficient mice
    Francesca Walker
    Ludwig Institute for Cancer Research, Melbourne Tumor Biology Branch, Melbourne, Victoria, Australia
    Blood 111:3978-85. 2008
    ..NPA production by mice defective for both G-CSF and GM-CSF uncovers an alternative pathway to granulocyte production, which is activated after exposure to pathogens...
  90. pmc The transcription factor IFN regulatory factor-4 controls experimental colitis in mice via T cell-derived IL-6
    Jonas Mudter
    1st Medical Clinic, University of Mainz, Mainz, Germany
    J Clin Invest 118:2415-26. 2008
    ..Taken together, our data identify IRF4 as a key regulator of mucosal IL-6 production in T cell-dependent experimental colitis and suggest that IRF4 might provide a therapeutic target for IBDs...
  91. ncbi request reprint Sleep enhances IL-6 trans-signaling in humans
    Stoyan Dimitrov
    Department of Neuroendocrinology, University of Lubeck, Ratzeburger Allee 160, Haus 23a, Lubeck 23538, Germany
    FASEB J 20:2174-6. 2006
    ..The selective increase in sIL-6R implicates an enhanced trans-signaling capacity whereby sleep distinctly widens the profile of IL-6 actions, enabling an integrated influence on brain and peripheral organs...
  92. ncbi request reprint Maintenance of pluripotency in human embryonic stem cells is STAT3 independent
    Rohan K Humphrey
    The Islet Research Laboratory, Whittier Institute for Diabetes, Department of Pediatrics, School of Medicine, 9894 Genesee Ave, University of California San Diego, La Jolla 92037, USA
    Stem Cells 22:522-30. 2004
    ..Furthermore, the data demonstrate the existence of an as-yet-unidentified factor in the conditioned media of mouse feeder layer cells that acts to maintain hES cell renewal in a STAT3-independent manner...
  93. ncbi request reprint Genetic manipulations utilizing albumin and alpha-fetoprotein promoter/enhancers affect both hepatocytes and oval cells
    Vance B Matthews
    Hepatology 40:759; author reply 760. 2004
  94. ncbi request reprint TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling
    Christoph Becker
    Laboratory of Immunology, I Medical Clinic, University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany
    Immunity 21:491-501. 2004
    ..Taken together, our data provide novel insights into TGF-beta signaling in colorectal cancer and suggest novel therapeutic approaches for colorectal cancer based on inhibition of TGF-beta-dependent IL-6 trans-signaling...
  95. ncbi request reprint Virokines in the pathogenesis of cancer: focus on human herpesvirus 8
    Mariam Klouche
    Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Germany
    Ann N Y Acad Sci 1028:329-39. 2004
    ..We provide an overview of the role of virokines in cancer, with a particular focus on the differences of human and viral IL-6 in the pathophysiology of HHV8-associated tumors...
  96. pmc Dynamics of the gp130 cytokine complex: a model for assembly on the cellular membrane
    Andreas Schroers
    Evotec Technologies GmbH, D 40225 Dusseldorf, Germany
    Protein Sci 14:783-90. 2005
    ..This view contrasts with the current perception of IL-6 receptor activation and reveals an alternative receptor activation mechanism...
  97. pmc The IL-6R alpha chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo
    Aysefa Doganci
    Laboratory of Cellular and Molecular Immunology of the Lung, First Medical Clinic, University of Mainz, Mainz, Germany
    J Clin Invest 115:313-25. 2005
    ..Furthermore, inhibition of IL-6 signaling emerges as a novel molecular approach for the treatment of allergic asthma...
  98. pmc IL-6/IL-6R axis plays a critical role in acute kidney injury
    Yael Nechemia-Arbely
    Goldyne Savad Institute of Gene Therapy, Jerusalem, 91120, Israel
    J Am Soc Nephrol 19:1106-15. 2008
    ..In summary, IL-6 simultaneously promotes an injurious inflammatory response and, through a mechanism of trans-signaling, protects the kidney from further injury...
  99. ncbi request reprint Interleukin-31 and oncostatin-M mediate distinct signaling reactions and response patterns in lung epithelial cells
    Souvik Chattopadhyay
    Department of Molecular and Cellular Biology and Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA
    J Biol Chem 282:3014-26. 2007
    ..The data suggest that inflammatory and immune reactions involving activated T-cells regulate functions of epithelial cells by IL-6 cytokines through receptor-defined signaling reactions...
  100. ncbi request reprint CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK
    Matthew J Watt
    Cellular and Molecular Metabolism Laboratory, School of Medical Sciences, Royal Melbourne Institute of Technology, PO Box 71, Bundoora, 3083, Australia
    Nat Med 12:541-8. 2006
    ....