Antiflammin-2 Activates the Human Formyl-Peptide Receptor Like 1

The anti-inflammatory actions of the nonapeptide antiflammin-2, identified by homology with uteroglobin and annexin-A1 sequences, have been described in some detail, yet its mechanisms of action remain elusive. Since recent data indicate an involvement of the formyl peptide receptor (FPR)-like 1 (or...

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Main Authors: Ahmad M. Kamal, Richard P.G. Hayhoe, Anbalakan Paramasivam, Dianne Cooper, Roderick J. Flower, Egle Solito, Mauro Perretti
Format: Article
Language:English
Published: Wiley 2006-01-01
Series:The Scientific World Journal
Online Access:http://dx.doi.org/10.1100/tsw.2006.247
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author Ahmad M. Kamal
Richard P.G. Hayhoe
Anbalakan Paramasivam
Dianne Cooper
Roderick J. Flower
Egle Solito
Mauro Perretti
author_facet Ahmad M. Kamal
Richard P.G. Hayhoe
Anbalakan Paramasivam
Dianne Cooper
Roderick J. Flower
Egle Solito
Mauro Perretti
author_sort Ahmad M. Kamal
collection DOAJ
description The anti-inflammatory actions of the nonapeptide antiflammin-2, identified by homology with uteroglobin and annexin-A1 sequences, have been described in some detail, yet its mechanisms of action remain elusive. Since recent data indicate an involvement of the formyl peptide receptor (FPR)-like 1 (or FPRL-1) in the effects of annexin-A1, we have tested here the effect of antiflammin-2 with respect to this receptor family. Using HEK-293 cells expressing either human FPR and FPRL-1, and an annexin-A1 peptide as tracer ([125I-Tyr]-Ac2-26), we found that antiflammin-2 competed for binding only at FPRL-1, and not FPR, with an approximate EC50 of 1 μM. In line with data produced for the full-length protein, genuine receptor activation by antiflammin-2 was confirmed by rapid phosphorylation of extracellular-regulated kinase 1 and 2. Finally, study of the neutrophil interaction with activated endothelium under flow demonstrated an inhibitory effect of antiflammin-2, thus providing functional support to a role for the antiflammin-2/FPRL-1 anti-inflammatory axis.
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institution Kabale University
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publishDate 2006-01-01
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spelling doaj-art-f5939587e79f46a59d0e9f2b49c69f482025-02-03T07:25:43ZengWileyThe Scientific World Journal1537-744X2006-01-0161375138410.1100/tsw.2006.247Antiflammin-2 Activates the Human Formyl-Peptide Receptor Like 1Ahmad M. Kamal0Richard P.G. Hayhoe1Anbalakan Paramasivam2Dianne Cooper3Roderick J. Flower4Egle Solito5Mauro Perretti6William Harvey Research Institute, Charterhouse Square, London EC1M 6BQ, UKWilliam Harvey Research Institute, Charterhouse Square, London EC1M 6BQ, UKWilliam Harvey Research Institute, Charterhouse Square, London EC1M 6BQ, UKWilliam Harvey Research Institute, Charterhouse Square, London EC1M 6BQ, UKWilliam Harvey Research Institute, Charterhouse Square, London EC1M 6BQ, UKDivision of Neuroscience and Mental Health Imperial College London Hammersmith Hospital Campus, London W12 0NN, UKWilliam Harvey Research Institute, Charterhouse Square, London EC1M 6BQ, UKThe anti-inflammatory actions of the nonapeptide antiflammin-2, identified by homology with uteroglobin and annexin-A1 sequences, have been described in some detail, yet its mechanisms of action remain elusive. Since recent data indicate an involvement of the formyl peptide receptor (FPR)-like 1 (or FPRL-1) in the effects of annexin-A1, we have tested here the effect of antiflammin-2 with respect to this receptor family. Using HEK-293 cells expressing either human FPR and FPRL-1, and an annexin-A1 peptide as tracer ([125I-Tyr]-Ac2-26), we found that antiflammin-2 competed for binding only at FPRL-1, and not FPR, with an approximate EC50 of 1 μM. In line with data produced for the full-length protein, genuine receptor activation by antiflammin-2 was confirmed by rapid phosphorylation of extracellular-regulated kinase 1 and 2. Finally, study of the neutrophil interaction with activated endothelium under flow demonstrated an inhibitory effect of antiflammin-2, thus providing functional support to a role for the antiflammin-2/FPRL-1 anti-inflammatory axis.http://dx.doi.org/10.1100/tsw.2006.247
spellingShingle Ahmad M. Kamal
Richard P.G. Hayhoe
Anbalakan Paramasivam
Dianne Cooper
Roderick J. Flower
Egle Solito
Mauro Perretti
Antiflammin-2 Activates the Human Formyl-Peptide Receptor Like 1
The Scientific World Journal
title Antiflammin-2 Activates the Human Formyl-Peptide Receptor Like 1
title_full Antiflammin-2 Activates the Human Formyl-Peptide Receptor Like 1
title_fullStr Antiflammin-2 Activates the Human Formyl-Peptide Receptor Like 1
title_full_unstemmed Antiflammin-2 Activates the Human Formyl-Peptide Receptor Like 1
title_short Antiflammin-2 Activates the Human Formyl-Peptide Receptor Like 1
title_sort antiflammin 2 activates the human formyl peptide receptor like 1
url http://dx.doi.org/10.1100/tsw.2006.247
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