Cited by 372Chemokine receptors and signalingImmune Response and InflammationInflammation biomarkers and pathways

Synthetic chemerin-derived peptides suppress inflammation through ChemR23

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Cash, Jenna L., Hart, Rosie, Russ, Andreas, Dixon, John P.C., Colledge, William H., Doran, Joanne, Hendrick, Alan G., Carlton, Mark B.L. +1 more·2008·The Journal of Experimental Medicine

Abstract

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; A140-A154), inhibited macrophage (MΦ) activation to a similar extent as proteolyzed chemerin, but exhibited reduced activity as a MΦ 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.

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Authors
Cash, J. L., Hart, R., Russ, A., Dixon, J. P. C., Colledge, W. H., Doran, J., Hendrick, A. G., Carlton, M. B. L., & Greaves, D. R.
Affiliations
  • University of Oxford (GB)
  • Takeda (United Kingdom) (GB)
Venue
The Journal of Experimental Medicine
Published
2008-04-07
Volume
205
Issue
4
Pages
767-775
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
OpenAlex
W2107653986
Cited by
372
References
25
Citations by year
2026: 12 · 2025: 9 · 2024: 18 · 2023: 14 · 2022: 20 · 2021: 17 · 2020: 14 · 2019: 21 · 2018: 21 · 2017: 18 · 2016: 21 · 2015: 29 · 2014: 23 · 2013: 22 · 2012: 26
FWCI
15.34
Type
journal article
Language
en
Open access
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Explore Bristol Research (publishedVersion)
  • Bristol Research (University of Bristol) (submittedVersion)
  • Apollo (University of Cambridge) (submittedVersion)
  • Apollo
Funders
British Heart Foundation
Topics
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Keywords
chemerin, ChemR23, anti-inflammatory peptides, G protein-coupled receptors, proteolytic processing, macrophage activation, neutrophil recruitment, monocyte recruitment, zymosan-induced peritonitis, peritonitis, chemotaxis, inflammatory diseases
MeSH terms
Animals, Anti-Inflammatory Agents, Antibodies, Chemotactic Factors, Chemotaxis, Inflammation, Macrophage Activation, Mice, Inbred C57BL, Neutralization Tests, Peptides, Peritonitis, Protein Processing, Post-Translational, Zymosan, Macrophages, Peritoneal, Chemokines, Receptors, Chemokine, Intercellular Signaling Peptides and Proteins, Receptors, G-Protein-Coupled, Mice

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