Journal ArticleDOI
An antibody to a 17 amino acid synthetic peptide of the type I interleukin-1 receptor preferentially blocks interleukin-1 beta binding.
Burton D. Clark,Takashi Ikejima,Javier Mancilla,Scott F. Orencole,Steven P. Sirko,Norihisa Ishii,Kenji Okuda,Charles A. Dinarello +7 more
TLDR
It is suggested that antibody to a specific epitope on the extracellular domain interferes with the binding ofIL-1 beta but not IL-1 alpha, and the differential inhibition of binding of IL- 1 beta butNot IL-2 alpha by anti-IL- 1RI150-166 also blocks biologic activity.Abstract:
On the basis of their relative hydropathy and α-helical structure, we prepared antibodies to four synthetic peptides with amino acid sequences homologous to four hydrophilic, extracellular regions of the murine 80 kDa type I interleukin-1 receptor (IL-1RI). Antibodies to each of the four peptides recognized their specific immunogen. Human [125I]-IL-lα or -β was crosslinked to murine EL4 and D10S cells. Antiserum to peptide 150-166 precipitated the IL-1/IL-1R complex, whereas antibodies to peptide 66-84, 190-200, or 266-285 did not. Antibody to peptide 150-166 did not precipitate the type II IL-1R. Anti-IL-1RI150-166 blocked 71% of the binding of radiolabeled human IL-1β to EL4 cells and 50% of the binding to D10S cells. Using affinity-purified anti-IL-1RI150-166, we compared the ability of this antibody to inhibit the binding of murine or human IL-1α to that of murine or human IL-1β. At a concentration of 20 ng/ml, affinity-purified anti-IL-1RI150-166 blocked 50% binding of murine IL-1β. At 1 μg/ml, 90% b...read more
Citations
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Journal ArticleDOI
Structural requirements of six naturally occurring isoforms of the IL-18 binding protein to inhibit IL-18
Soohyun Kim,Miriam Eisenstein,Leonid L. Reznikov,Giamila Fantuzzi,Daniela Novick,Menachem Rubinstein,Charles A. Dinarello +6 more
TL;DR: A novel, constitutively expressed and secreted IL-18 binding protein (IL-18BP) neutralizes IL- 18 and thereby suppresses the production of IFN-gamma, resulting in reduced T-helper type 1 immune responses.
Journal ArticleDOI
Model of interaction of the IL-1 receptor accessory protein IL-1RAcP with the IL-1β/IL-1RI complex
Rita Casadio,Elisabetta Frigimelica,Paola Bossù,Detlef Neumann,Michael U. Martin,Aldo Tagliabue,Diana Boraschi +6 more
TL;DR: Experimental data obtained with the use of IL‐1β peptides and antibodies, and with mutated IL-1β proteins, support the BACK model, in which IL‐ 1RAcP establishes contacts with the back of IL•1RI wrapped around IL‐2β.
Journal ArticleDOI
Targeting interleukin 18 with interleukin 18 binding protein
TL;DR: A novel, constitutively expressed and secreted interleukin 18 ( IL18) binding protein (IL18BP) neutralises IL18 and identifies a large mixed electrostatic and hydrophobic binding site in the immunoglobulin domain of IL18BP which could account for its high affinity binding to the ligand.
Journal ArticleDOI
Identification of a Critical Ig-Like Domain in IL-18 Receptor α and Characterization of a Functional IL-18 Receptor Complex
Tania Azam,Daniela Novick,Philip Bufler,Do-Young Yoon,Menachem Rubinstein,Charles A. Dinarello,Soohyun Kim,Soohyun Kim +7 more
TL;DR: The present studies demonstrate that the biologically active IL-18R complex requires the membrane-proximal third Ig-like domain in IL- 18Rα for the formation of IL-16R ternary complex as well as for signal transduction involved inIL-18-induced IFN-γ in NK cells.
Journal ArticleDOI
ACTIVATION OF NEUTRAL SPHINGOMYELINASE BY IL-1β REQUIRES THE TYPE 1 INTERLEUKIN 1 RECEPTOR
Natalia N. Nalivaeva,E. G. Rybakina,Irina Yu. Pivanovich,I. A. Kozinets,Sergei N. Shanin,Tamas Bartfai +5 more
TL;DR: The data suggest that nSMase, a key enzyme of the sphingomyelin signal transduction pathway, might be involved in IL-1beta signalling in the brain and that activation of the enzyme requires theIL-1 receptor type 1.
References
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Jack Kyte,Russell F. Doolittle +1 more
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TL;DR: The preliminary results of clinical trials in humans indicate possible efficacy of IL-1ra in sepsis syndrome, rheumatoid arthritis, and GVHD, and some animal models of septic shock, inflammatory arthritis, graft-versus-host disease and inflammatory bowel disease.
Journal ArticleDOI
A novel IL-1 receptor, cloned from B cells by mammalian expression, is expressed in many cell types.
Catherine J. McMahan,J.L. Slack,B. Mosley,David Cosman,Stephen D. Lupton,L.L. Brunton,C E Grubin,J M Wignall,Nancy A. Jenkins,C.I. Brannan +9 more
TL;DR: The use of an improved expression cloning method is used to isolate human and murine cDNA clones encoding a second type of IL‐1 receptor (type II receptor), which appears to be well conserved in evolution and map to the same chromosomal location.