Abstract
Soluble gp130 is the natural inhibitor of trans-signaling mediated by the soluble IL-6/IL-6R complex. In mouse models, recombinant sgp130 has been successfully applied for the treatment of diseases that are triggered and maintained by soluble IL-6R like Crohn's disease, peritonitis, rheumatoid arthritis, and colon cancer. The novel heterodimeric cytokine IL-27 (p28/EBV-induced gene 3) has been shown to act via a heterodimeric receptor complex of gp130 and the WSX-1 receptor, and to co-regulate the Th(1) immune response after infection. Therefore, we have tested the potential of the recombinant sgp130-Fc protein to also inhibit signaling-mediated IL-27. 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / chemistry
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Antigens, CD / genetics
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Antigens, CD / metabolism
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Antigens, CD / pharmacology*
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Bone Marrow Cells / drug effects
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Bone Marrow Cells / metabolism*
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Cell Line
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Cytokine Receptor gp130
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DNA-Binding Proteins / metabolism*
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Dose-Response Relationship, Drug
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Humans
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Interleukin-6 / metabolism*
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Interleukins / metabolism*
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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Membrane Glycoproteins / pharmacology*
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Mice
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Recombinant Proteins / metabolism
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Recombinant Proteins / pharmacology
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STAT3 Transcription Factor
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Signal Transduction / drug effects*
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Signal Transduction / physiology*
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Solubility
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Trans-Activators / metabolism*
Substances
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Antigens, CD
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DNA-Binding Proteins
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IL6ST protein, human
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Il27 protein, mouse
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Il6st protein, mouse
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Interleukin-6
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Interleukins
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Membrane Glycoproteins
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Recombinant Proteins
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STAT3 Transcription Factor
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STAT3 protein, human
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Stat3 protein, mouse
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Trans-Activators
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Cytokine Receptor gp130