Antiflammin-2 Activates the Human Formyl-Peptide Receptor Like 1. (2006)

• Record Type: Journal Article
• Authors: Kamal, Ahmad M.; Hayhoe, Richard P.G.; Paramasivam, Anbalakan; Cooper, Dianne; Flower, Roderick J.; Solito, Egle; Perretti, Mauro
• Other Names: Wallace John L. Academic Editor.
• Is Part Of: TheScientificWorldjournal. Volume 6(2006)
• Page Start: 1375
• Page End: 1384
• Publication Date: 2006
• Subjects: anti-inflammation -- antiflammin -- annexin 1 -- FPRL-1 -- formyl peptide receptors -- binding -- anti-inflammatory drugs -- drug development -- neutrophil -- PMN -- inflammation -- lipocortin -- annexin-A1 -- ALX -- anti-inflammatory agents -- peptides -- FPR -- signal transduction -- flow chamber; Science -- Periodicals; Technology -- Periodicals; Medicine -- Periodicals; 505
• DOI: 10.1100/tsw.2006.247
• Languages: English
• ISSNs: 2356-6140

Abstract

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 ([ 125 I-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.