Synthetic chemerin-derived peptides suppress inflammation through ChemR23

Jenna L Cash, Rosie Hart, Andreas Russ, John P C Dixon, William H Colledge, Joanne Doran, Alan G Hendrick, Mark B L Carlton, David R Greaves

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Chemerin is a chemotactic protein that binds to the G protein-coupled receptor, ChemR23. We demonstrate that murine chemerin possesses potent antiinflammatory properties that are absolutely dependent on proteolytic processing. A series of peptides was designed, and only those identical to specific C-terminal chemerin sequences exerted antiinflammatory effects at picomolar concentrations in vitro. One of these, chemerin15 (C15; A(140)-A(154)), inhibited macrophage (MPhi) activation to a similar extent as proteolyzed chemerin, but exhibited reduced activity as a MPhi chemoattractant. Intraperitoneal administration of C15 (0.32 ng/kg) to mice before zymosan challenge conferred significant protection against zymosan-induced peritonitis, suppressing neutrophil (63%) and monocyte (62%) recruitment with a concomitant reduction in proinflammatory mediator expression. Importantly, C15 was unable to ameliorate zymosan-induced peritonitis in ChemR23(-/-) mice, demonstrating that C15's antiinflammatory effects are entirely ChemR23 dependent. In addition, administration of neutralizing anti-chemerin antibody before zymosan challenge resulted in a significant exacerbation of peritoneal inflammation (up to 170%), suggesting an important endogenous antiinflammatory role for chemerin-derived species. Collectively, these results show that chemerin-derived peptides may represent a novel therapeutic strategy for the treatment of inflammatory diseases through ChemR23.

Original languageEnglish
Pages (from-to)767-75
Number of pages9
JournalJournal of Experimental Medicine
Issue number4
Publication statusPublished - 14 Apr 2008

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Anti-Inflammatory Agents
  • Antibodies
  • Chemokines
  • Chemotactic Factors
  • Chemotaxis
  • Inflammation
  • Intercellular Signaling Peptides and Proteins
  • Macrophage Activation
  • Macrophages, Peritoneal
  • Mice
  • Mice, Inbred C57BL
  • Neutralization Tests
  • Peptides
  • Peritonitis
  • Protein Processing, Post-Translational
  • Receptors, G-Protein-Coupled
  • Zymosan


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