No inhibition of IL-27 signaling by soluble gp130.
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.
Scheller
Jürgen
J
Institut für Biochemie, Christian-Albrechts Universität zu Kiel, Olshausenstr.40, D-24098 Kiel, Germany.
Schuster
Björn
B
Hölscher
Christoph
C
Yoshimoto
Takayuki
T
Rose-John
Stefan
S
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*; D012995:Solubility; D015534:Trans-Activators / Q000378:metabolism*
D015703:Antigens, CD; D004268:DNA-Binding Proteins; C494199:IL6ST protein, human; C486767:Il27 protein, mouse; C494200:Il6st protein, mouse; D015850:Interleukin-6; D007378:Interleukins; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D050822:Cytokine Receptor gp130