Synthetic chemerin-derived peptides suppress inflammation through ChemR23
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Pro-resolving ligands or inhibitors of CMKLR1 attenuate inflammatory responses, including neuroinflammation.
“Pro-resolving ligands or inhibitors of CMKLR1 have been shown to attenuate inflammatory responses, including neuroinflammation [156–158].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [157]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
MACROPHAGE RECEPTORS AND IMMUNE RECOGNITION
Taylor, P. R., Martínez‐Pomares, L., Stacey, M. A., Lin, H.-H., Brown, G. D., & Gordon, S. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115816 · Cited by 1,325 · see citing works
Resolvin E1 and protectin D1 activate inflammation-resolution programmes
Schwab, J. M., Chiang, N., Arita, M., & Serhan, C. N. (2007) · Nature · doi:10.1038/nature05877 · Cited by 1,188 · see citing works
Arita, M., Bianchini, F., Aliberti, J., Sher, A., Chiang, N., Hong, S., Yang, R., Petasis, N. A., & Serhan, C. N. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20042031 · Cited by 926 · see citing works
Wittamer, V., Franssen, J.-D., Vulcano, M., Mirjolet, J.-F., Le Poul, E., Migeotte, I., Brézillon, S., Tyldesley, R., Blanpain, C., Detheux, M., et al. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030382 · Cited by 888 · see citing works
Anti-inflammatory lipid mediators and insights into the resolution of inflammation
Lawrence, T., Willoughby, D. A., & Gilroy, D. W. (2002) · Nature reviews. Immunology · doi:10.1038/nri915 · Cited by 863 · see citing works
The genetic design of signaling cascades to record receptor activation
Barnea, G., Strapps, W. R., Herrada, G., Berman, Y. L., Ong, J., Kloss, B., Axel, R., & Lee, K. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710487105 · Cited by 673 · see citing works
Arita, M., Ohira, T., Sun, Y., Elangovan, S., Chiang, N., & Serhan, C. N. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.6.3912 · Cited by 636 · see citing works
Arita, M., Yoshida, M., Hong, S., Tjonahen, E., Glickman, J. N., Petasis, N. A., Blumberg, R. S., & Serhan, C. N. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409271102 · Cited by 590 · see citing works
Chemerin Activation by Serine Proteases of the Coagulation, Fibrinolytic, and Inflammatory Cascades
Zabel, B. A., Allen, S. J., Kulig, P., Allen, J. A., Cichy, J., Handel, T. M., & Butcher, E. C. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504868200 · Cited by 369 · see citing works
Limiting inflammatory responses during activation of innate immunity
Han, J., & Ulevitch, R. J. (2005) · Nature Immunology · doi:10.1038/ni1274 · Cited by 314 · see citing works
Rapid recruitment of inflammatory monocytes is independent of neutrophil migration
Henderson, R. B., Hobbs, J. A. R., Mathies, M., & Hogg, N. (2003) · Blood · doi:10.1182/blood-2002-10-3228 · Cited by 309 · see citing works
Neutrophil-Mediated Maturation of Chemerin: A Link between Innate and Adaptive Immunity
Wittamer, V., Bondue, B., Guillabert, A., Vassart, G., Parmentier, M., & Communi, D. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.1.487 · Cited by 247 · see citing works
Movat, H. Z., Cybulsky, M. I., Colditz, I. G., et al. (1987) · PubMed · Cited by 209 · see citing works
Wittamer, V., Grégoire, F., Robberecht, P., Vassart, G., Communi, D., & Parmentier, M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313016200 · Cited by 206 · see citing works
Characterization of human circulating TIG2 as a ligand for the orphan receptor ChemR23
Meder, W., Wendland, M., Busmann, A., Kutzleb, C., Spodsberg, N., John, H., Richter, R., Schleuder, D., Meyer, M., & Forssmann, W. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)01312-7 · Cited by 205 · see citing works
Role of natural killer cells and TCRγ δ T cells in acute autoimmune encephalomyelitis
Matsumoto, Y., Kohyama, K., Aikawa, Y., Shin, T., Kawazoe, Y., Suzuki, Y., & Tanuma, N. (1998) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(199805)28:05 · Cited by 157 · see citing works
Chemoattractants, extracellular proteases, and the integrated host defense response
Zabel, B. A., Zuniga, L. A., Ohyama, T., Allen, S. J., Cichy, J., Handel, T. M., & Butcher, E. C. (2006) · Experimental Hematology · doi:10.1016/j.exphem.2006.05.003 · Cited by 142 · see citing works
Chemokine-like receptor 1 expression by macrophages in vivo: Regulation by TGF-β and TLR ligands
Zabel, B. A., Ohyama, T., Zuniga, L. A., Kim, J., Johnston, B., Allen, S. J., Guido, D., Handel, T. M., & Butcher, E. C. (2006) · Experimental Hematology · doi:10.1016/j.exphem.2006.03.011 · Cited by 138 · see citing works
Taylor, P. R., Reid, D. M., Heinsbroek, S. E. M., Brown, G. D., Gordon, S., & Wong, S. Y. C. (2005) · European Journal of Immunology · doi:10.1002/eji.200425785 · Cited by 134 · see citing works
Inhibition of neutrophil and monocyte recruitment by endogenous and exogenous lipocortin 1
Getting, S. J., Flower, R. J., & Perretti, M. (1997) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0701029 · Cited by 130 · see citing works
Damazo, A. S., Yona, S., Flower, R. J., Perretti, M., & Oliani, S. M. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.7.4410 · Cited by 114 · see citing works
Calcium mobilization in Jurkat cells via A2b adenosine receptors
Mirabet, M., Mallol, J., Lluís, C., et al. (1997) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0701495 · Cited by 70 · see citing works
Neutrophil Emigration and Microvascular Injury
Movat, H. Z., & Cybulsky, M. I. (2008) · Pathology and Immunopathology Research · doi:10.1159/000157043 · Cited by 30 · see citing works
Choi, J., Brummer, E., Kang, Y. J., Jones, P. P., & Stevens, D. A. (2006) · The Journal of Infectious Diseases · doi:10.1086/500948 · Cited by 26 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Adipose tissue inflammation and metabolic dysfunction in obesity
Kawai, T., Autieri, M. V., & Scalia, R. (2021) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00379.2020 · Cited by 1,947 · see citing works
Phagocyte partnership during the onset and resolution of inflammation
Soehnlein, O., & Lindbom, L. (2010) · Nature Reviews Immunology · doi:10.1038/nri2779 · Cited by 1,054 · see citing works
Maresins: Novel macrophage mediators with potent antiinflammatory and proresolving actions
Serhan, C. N., Yang, R., Martinod, K., Kasuga, K., Pillai, P. S., Porter, T. F., Oh, S. F., & Spite, M. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20081880 · Cited by 908 · see citing works
Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation
Chen, Y., & Yu, Y. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02853-3 · Cited by 516 · see citing works
Novel Lipid Mediators and Resolution Mechanisms in Acute Inflammation
Serhan, C. N. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.100322 · Cited by 421 · see citing works
Chemerin and its receptors in leukocyte trafficking, inflammation and metabolism
Bondue, B., Wittamer, V., & Parmentier, M. (2011) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2011.11.004 · Cited by 294 · see citing works
El Kebir, D., Gjorstrup, P., & Filep, J. G. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1206641109 · Cited by 289 · see citing works
Resolvin E1 Receptor Activation Signals Phosphorylation and Phagocytosis
Ohira, T., Arita, M., Omori, K., Recchiuti, A., Van Dyke, T. E., & Serhan, C. N. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.044131 · Cited by 278 · see citing works
Recinella, L., Orlando, G., Ferrante, C., Chiavaroli, A., Brunetti, L., & Leone, S. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.578966 · Cited by 261 · see citing works
Update on leukotriene, lipoxin and oxoeicosanoid receptors: IUPHAR Review 7
Bäck, M., Powell, W. S., Dahlén, S., Drazen, J. M., Evans, J. F., Serhan, C. N., Shimizu, T., Yokomizo, T., & Rovati, G. E. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12665 · Cited by 217 · see citing works
Herová, M., Schmid, M., Gemperle, C., & Hersberger, M. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402166 · Cited by 157 · see citing works
Receptors for pro‐resolving mediators are increased in Alzheimer's disease brain
Emre, C., Hjorth, E., Bharani, K., Carroll, S., Granholm, A., & Schultzberg, M. (2020) · Brain Pathology · doi:10.1111/bpa.12812 · Cited by 60 · see citing works
Hepatic chemerin <scp>mRNA</scp> expression is reduced in human nonalcoholic steatohepatitis
Pohl, R., Haberl, E. M., Rein‐Fischboeck, L., Zimny, S., Neumann, M., Aslanidis, C., Schacherer, D., Krautbauer, S., Eisinger, K., Weiss, T. S., et al. (2017) · European Journal of Clinical Investigation · doi:10.1111/eci.12695 · Cited by 45 · see citing works
Zhang, R.-L., Wang, Q.-Q., Zhang, J.-P., & Yang, L.-J. (2017) · PLoS ONE · doi:10.1371/journal.pone.0175477 · Cited by 39 · see citing works
Zhang, H., Lin, A., Gong, P., Chen, Y., Ye, R. D., Qian, F., Zhang, Y., & Yu, Y. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.0455-20.2020 · Cited by 24 · see citing works
Lei, Z., Lu, Y., Bai, X., Jiang, Z., & Yu, Q. (2020) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b19-00510 · Cited by 23 · see citing works
Chen, Y., Liu, Z., Gong, P., Zhang, H., Chen, Y., Yao, S., Li, W., Zhang, Y., & Yu, Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23169041 · Cited by 25 · see citing works
- 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
- Publisher
- Rockefeller University Press
- Published
- 2008-04-07
- Volume
- 205
- Issue
- 4
- Pages
- 767-775
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2292217
- 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
- bronze
- doi.org
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review