Synthetic chemerin-derived peptides suppress inflammation through ChemR23

J Exp Med. 2008 Apr 14;205(4):767-75. doi: 10.1084/jem.20071601. Epub 2008 Apr 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antibodies / pharmacology
  • Chemokines
  • Chemotactic Factors / pharmacology*
  • Chemotactic Factors / therapeutic use
  • Chemotaxis / drug effects
  • Inflammation / drug therapy
  • Inflammation / pathology*
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • Intercellular Signaling Peptides and Proteins / therapeutic use
  • Macrophage Activation / drug effects
  • Macrophages, Peritoneal / cytology
  • Macrophages, Peritoneal / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Neutralization Tests
  • Peptides / pharmacology*
  • Peritonitis / pathology
  • Protein Processing, Post-Translational / drug effects
  • Receptors, Chemokine
  • Receptors, G-Protein-Coupled / deficiency
  • Receptors, G-Protein-Coupled / metabolism*
  • Zymosan


  • Anti-Inflammatory Agents
  • Antibodies
  • CMKLR1 protein, mouse
  • Chemokines
  • Chemotactic Factors
  • Intercellular Signaling Peptides and Proteins
  • Peptides
  • Receptors, Chemokine
  • Receptors, G-Protein-Coupled
  • chemerin protein, mouse
  • Zymosan