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Synthetic chemerin-derived peptides suppress inflammation through ChemR23

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...

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Autores principales: Cash, Jenna L., Hart, Rosie, Russ, Andreas, Dixon, John P.C., Colledge, William H., Doran, Joanne, Hendrick, Alan G., Carlton, Mark B.L., Greaves, David R.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2292217/
https://www.ncbi.nlm.nih.gov/pubmed/18391062
http://dx.doi.org/10.1084/jem.20071601
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author Cash, Jenna L.
Hart, Rosie
Russ, Andreas
Dixon, John P.C.
Colledge, William H.
Doran, Joanne
Hendrick, Alan G.
Carlton, Mark B.L.
Greaves, David R.
author_facet Cash, Jenna L.
Hart, Rosie
Russ, Andreas
Dixon, John P.C.
Colledge, William H.
Doran, Joanne
Hendrick, Alan G.
Carlton, Mark B.L.
Greaves, David R.
author_sort Cash, Jenna L.
collection PubMed
description 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 (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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spelling pubmed-22922172008-10-14 Synthetic chemerin-derived peptides suppress inflammation through ChemR23 Cash, Jenna L. Hart, Rosie Russ, Andreas Dixon, John P.C. Colledge, William H. Doran, Joanne Hendrick, Alan G. Carlton, Mark B.L. Greaves, David R. J Exp Med Brief Definitive Reports 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 (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. The Rockefeller University Press 2008-04-14 /pmc/articles/PMC2292217/ /pubmed/18391062 http://dx.doi.org/10.1084/jem.20071601 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Reports
Cash, Jenna L.
Hart, Rosie
Russ, Andreas
Dixon, John P.C.
Colledge, William H.
Doran, Joanne
Hendrick, Alan G.
Carlton, Mark B.L.
Greaves, David R.
Synthetic chemerin-derived peptides suppress inflammation through ChemR23
title Synthetic chemerin-derived peptides suppress inflammation through ChemR23
title_full Synthetic chemerin-derived peptides suppress inflammation through ChemR23
title_fullStr Synthetic chemerin-derived peptides suppress inflammation through ChemR23
title_full_unstemmed Synthetic chemerin-derived peptides suppress inflammation through ChemR23
title_short Synthetic chemerin-derived peptides suppress inflammation through ChemR23
title_sort synthetic chemerin-derived peptides suppress inflammation through chemr23
topic Brief Definitive Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2292217/
https://www.ncbi.nlm.nih.gov/pubmed/18391062
http://dx.doi.org/10.1084/jem.20071601
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