Synthetic chemerin-derived peptides suppress inflammation through ChemR23.

Journal article

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.

Authors: Cash, J; Hart, R; Russ, A; Dixon, J; Colledge, W

• Publication status: Published
• Journal: Journal of experimental medicine
• Volume: 205
• Issue: 4
• Pages: 767-775
• Publication date: 2008-04-01
• DOI: 10.1084/jem.20071601
• EISSN: 1540-9538
• ISSN: 0022-1007
• Language: English
• Keywords: Antibodies; Neutralization Tests; Mice, Inbred C57BL; Zymosan; Macrophages, Peritoneal; Peritonitis; Animals; Mice; Chemotaxis; Chemotactic Factors; Peptides; Macrophage Activation; Inflammation; Intercellular Signaling Peptides and Proteins; Receptors, G-Protein-Coupled; Protein Processing, Post-Translational; Anti-Inflammatory Agents