Abstract
An interleukin-18 binding protein (IL-18BP) was purified from urine by chromatography on IL-18 beads, sequenced, cloned, and expressed in COS7 cells. IL-18BP abolished IL-18 induction of interferon-gamma (IFNgamma), IL-8, and activation of NF-kappaB in vitro. Administration of IL-18BP to mice abrogated circulating IFNgamma following LPS. Thus, IL-18BP functions as an inhibitor of the early Th1 cytokine response. IL-18BP is constitutively expressed in the spleen, belongs to the immunoglobulin superfamily, and has limited homology to the IL-1 type II receptor. Its gene was localized on human chromosome 11q13, and no exon coding for a transmembrane domain was found in an 8.3 kb genomic sequence. Several Poxviruses encode putative proteins highly homologous to IL-18BP, suggesting that viral products may attenuate IL-18 and interfere with the cytotoxic T cell response.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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COS Cells
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Carrier Proteins / genetics
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Carrier Proteins / isolation & purification
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Carrier Proteins / physiology*
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Carrier Proteins / urine
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Cloning, Molecular
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Cytokines / biosynthesis*
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DNA, Complementary / isolation & purification
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Exons
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Humans
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Injections, Intraperitoneal
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Interferon Inducers / antagonists & inhibitors
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Interferon-gamma / antagonists & inhibitors
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Interferon-gamma / biosynthesis
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Interleukin-18 / antagonists & inhibitors
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Interleukin-18 / metabolism*
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Interleukin-18 / physiology
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Introns
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Lipopolysaccharides / antagonists & inhibitors
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Lipopolysaccharides / pharmacology
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Mice
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Molecular Sequence Data
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Poxviridae / genetics
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Recombinant Proteins / administration & dosage
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Sequence Homology, Amino Acid
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Spleen / metabolism
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Th1 Cells / metabolism*
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Viral Proteins / genetics
Substances
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Carrier Proteins
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Cytokines
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DNA, Complementary
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Interferon Inducers
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Interleukin-18
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Lipopolysaccharides
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Recombinant Proteins
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Viral Proteins
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Interferon-gamma
Associated data
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GENBANK/AF110460
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GENBANK/AF110798
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GENBANK/AF110799
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GENBANK/AF110800
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GENBANK/AF110801
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GENBANK/AF110802
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GENBANK/AF110803