title: Antiflammin-2 activates the human formyl-peptide receptor like 1.
abstract: 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 mM. 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.
authors.affiliation: The William Harvey Research Institute, Charterhouse Square, London EC1M 6BQ, U.K. ahmad.kamal@tech.mrc.ac.uk
authors.forename: Ahmad M
authors.initials: AM
authors.lastname: Kamal
authors.forename: Richard P G
authors.initials: RP
authors.lastname: Hayhoe
authors.forename: Anbalakan
authors.initials: A
authors.lastname: Paramasivam
authors.forename: Dianne
authors.initials: D
authors.lastname: Cooper
authors.forename: Roderick J
authors.initials: RJ
authors.lastname: Flower
authors.forename: Egle
authors.initials: E
authors.lastname: Solito
authors.forename: Mauro
authors.initials: M
authors.lastname: Perretti
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001667:Binding, Competitive; D002478:Cells, Cultured; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000196:embryology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation; D044042:Receptors, Formyl Peptide / Q000187:drug effects* / Q000502:physiology; D044067:Receptors, Lipoxin / Q000187:drug effects* / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C105101:FPR2 protein, human; D009842:Oligopeptides; D010446:Peptide Fragments; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C064647:antiflammin P2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3