title: A novel cytokine receptor-ligand pair. Identification, molecular characterization, and in vivo immunomodulatory activity.
abstract: As part of a large scale effort to discover novel secreted proteins, a cDNA encoding a novel cytokine was identified. Alignments of the sequence of the new protein, designated IL-17B, suggest it to be a homolog of the recently described T cell-derived cytokine, IL-17. By Northern analysis, EST distribution and real-time quantitative polymerase chain reaction analysis, mRNA was detected in many cell types. A novel type I transmembrane protein, identified in an EST data base by homology to IL-17R, was found to bind specifically IL-17B, as determined by surface plasmon resonance analysis, flow cytometry, and co-immunoprecipitation experiments. Readily detectable transcription of IL-17BR was restricted to human kidney, pancreas, liver, brain, and intestines and only a few of the many cell lines tested. By using a rodent ortholog of IL-17BR as a probe, IL-17BR message was found to be drastically up-regulated during intestinal inflammation elicited by indomethacin treatment in rats. In addition, intraperitoneal injection of IL-17B purified from Chinese hamster ovary cells caused marked neutrophil migration in normal mice, in a specific and dose-dependent manner. Together these results suggest that IL-17B may be a novel proinflammatory cytokine acting on a restricted set of target cell types. They also demonstrate the strength of genomic approaches in the unraveling of novel biological pathways.
authors.affiliation: Departments of Molecular Biology, Protein Development, Strategic Drug Development, and Cell Biology, Human Genome Sciences, Inc., Rockville, Maryland 20850, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
authors.forename: S J
authors.initials: SJ
authors.lastname: Ullrich
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: K
authors.initials: K
authors.lastname: Connolly
authors.forename: K J
authors.initials: KJ
authors.lastname: Grzegorzewski
authors.forename: M C
authors.initials: MC
authors.lastname: Barber
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Wathen
authors.forename: V
authors.initials: V
authors.lastname: Hodge
authors.forename: C L
authors.initials: CL
authors.lastname: Fisher
authors.forename: H
authors.initials: H
authors.lastname: Olsen
authors.forename: S M
authors.initials: SM
authors.lastname: Ruben
authors.forename: I
authors.initials: I
authors.lastname: Knyazev
authors.forename: Y H
authors.initials: YH
authors.lastname: Cho
authors.forename: V
authors.initials: V
authors.lastname: Kao
authors.forename: K A
authors.initials: KA
authors.lastname: Wilkinson
authors.forename: J A
authors.initials: JA
authors.lastname: Carrell
authors.forename: R
authors.initials: R
authors.lastname: Ebner
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002465:Cell Movement; D006224:Cricetinae; D018076:DNA, Complementary; D020224:Expressed Sequence Tags; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D018123:Receptors, Interleukin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D000276:Adjuvants, Immunologic; D018076:DNA, Complementary; C109985:IL17RA protein, human; C491673:Il17ra protein, mouse; D020381:Interleukin-17; D008024:Ligands; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins