| First Author | Cash JL | Year | 2008 |
| Journal | J Exp Med | Volume | 205 |
| Issue | 4 | Pages | 767-75 |
| PubMed ID | 18391062 | Mgi Jnum | J:133968 |
| Mgi Id | MGI:3784725 | Doi | 10.1084/jem.20071601 |
| Citation | Cash JL, et al. (2008) Synthetic chemerin-derived peptides suppress inflammation through ChemR23. J Exp Med 205(4):767-75 |
| abstractText | 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. |
