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A novel cytokine receptor-ligand pair. Identification, molecular characterization, and in vivo immunomodulatory activity.

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.

Pubmed ID: 10749887

Authors

  • Shi Y
  • Ullrich SJ
  • Zhang J
  • Connolly K
  • Grzegorzewski KJ
  • Barber MC
  • Wang W
  • Wathen K
  • Hodge V
  • Fisher CL
  • Olsen H
  • Ruben SM
  • Knyazev I
  • Cho YH
  • Kao V
  • Wilkinson KA
  • Carrell JA
  • Ebner R

Journal

The Journal of biological chemistry

Publication Data

June 23, 2000

Associated Grants

None

Mesh Terms

  • Adjuvants, Immunologic
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Cell Movement
  • Cricetinae
  • DNA, Complementary
  • Expressed Sequence Tags
  • Humans
  • Interleukin-17
  • Ligands
  • Mice
  • Molecular Sequence Data
  • Neutrophils
  • RNA, Messenger
  • Rats
  • Receptors, Interleukin
  • Receptors, Interleukin-17
  • Recombinant Proteins
  • Sequence Homology, Amino Acid