Source:http://linkedlifedata.com/resource/pubmed/id/11121117
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2001-1-23
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| pubmed:abstractText |
Signal transduction in response to interleukin-6 (IL-6) requires binding of the cytokine to its receptor (IL-6R) and subsequent homodimerization of the signal transducer gp130. The complex of IL-6 and soluble IL-6R (sIL-6R) triggers dimerization of gp130 and induces responses on cells that do not express membrane bound IL-6R. Naturally occurring soluble gp130 (sgp130) can be found in a ternary complex with IL-6 and sIL-6R. We created recombinant sgp130 proteins that showed binding to IL-6 in complex with sIL-6R and inhibited IL-6/sIL-6R induced proliferation of BAF/3 cells expressing gp130. Surprisingly, sgp130 proteins did not affect IL-6 stimulated proliferation of BAF/3 cells expressing gp130 and membrane bound IL-6R, indicating that sgp130 did not interfere with IL-6 bound to IL-6R on the cell surface. Additionally, sgp130 partially inhibited proliferation induced by leukemia inhibitory factor (LIF) and oncostatin M (OSM) albeit at higher concentrations. Recombinant sgp130 protein could be used to block the anti-apoptotic effect of sIL-6R on lamina propria cells from Crohn disease patients. We conclude that sgp130 is the natural inhibitor of IL-6 responses dependent on sIL-6R. Furthermore, recombinant sgp130 is expected to be a valuable therapeutic tool to specifically block disease states in which sIL-6R transsignaling responses exist, e.g. in morbus Crohn disease.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokine Receptor gp130,
http://linkedlifedata.com/resource/pubmed/chemical/IL6ST protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Il6st protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
0014-2956
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
268
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
160-7
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| pubmed:dateRevised |
2007-7-23
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| pubmed:meshHeading |
pubmed-meshheading:11121117-Acute-Phase Reaction,
pubmed-meshheading:11121117-Animals,
pubmed-meshheading:11121117-Antigens, CD,
pubmed-meshheading:11121117-Apoptosis,
pubmed-meshheading:11121117-Cell Division,
pubmed-meshheading:11121117-Cells, Cultured,
pubmed-meshheading:11121117-Crohn Disease,
pubmed-meshheading:11121117-Cytokine Receptor gp130,
pubmed-meshheading:11121117-Humans,
pubmed-meshheading:11121117-Leukocytes, Mononuclear,
pubmed-meshheading:11121117-Membrane Glycoproteins,
pubmed-meshheading:11121117-Mice,
pubmed-meshheading:11121117-Protein Synthesis Inhibitors,
pubmed-meshheading:11121117-Receptors, Interleukin-6,
pubmed-meshheading:11121117-Recombinant Proteins,
pubmed-meshheading:11121117-Signal Transduction,
pubmed-meshheading:11121117-Solubility,
pubmed-meshheading:11121117-Transfection,
pubmed-meshheading:11121117-Tumor Cells, Cultured
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| pubmed:year |
2001
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| pubmed:articleTitle |
Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor transsignaling responses.
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| pubmed:affiliation |
I. Medizinische Klinik, Section Pathophysiologie, Johannes Gutenberg Universität Mainz, Germany.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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