PMID- 23643932 OWN - NLM STAT- MEDLINE DCOM- 20130809 LR - 20131121 IS - 1873-2968 (Electronic) IS - 0006-2952 (Linking) VI - 85 IP - 12 DP - 2013 Jun 15 TI - Heterologously expressed formyl peptide receptor 2 (FPR2/ALX) does not respond to lipoxin A(4). PG - 1795-802 LID - S0006-2952(13)00261-X [pii] LID - 10.1016/j.bcp.2013.04.019 [doi] AB - Lipoxin A(4) (LXA(4)) has been described as an anti-inflammatory mediator, which exerts its effects through the formyl peptide receptor FPR2, also known as ALX. However, there has been a controversy whether or not cells expressing FPR2/ALX, such as neutrophils, respond to LXA(4). We, therefore, systematically examined the ability of the human and murine forms of the receptor to respond to LXA(4). We show that both receptor orthologues responded to the FPR2/ALX peptide agonist WKYMVM when expressed heterologously. In contrast, LXA(4) from different sources neither increased [Ca(2)(+)](i) and extracellular-signal-regulated kinase (ERK) phosphorylation, nor did it induce a decrease in cAMP levels or a translocation of beta-arrestin. Also, several LXA(4) analogs were found to be unable to signal through FPR2/ALX. We conclude that FPR2/ALX is not activated by LXA(4) and that the molecular mechanism by which LXA(4) functions still needs to be identified. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Hanson, Julien AU - Hanson J AD - Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany. j.hanson@ulg.ac.be FAU - Ferreiros, Nerea AU - Ferreiros N FAU - Pirotte, Bernard AU - Pirotte B FAU - Geisslinger, Gerd AU - Geisslinger G FAU - Offermanns, Stefan AU - Offermanns S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130501 PL - England TA - Biochem Pharmacol JT - Biochemical pharmacology JID - 0101032 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (FPR2 protein, human) RN - 0 (Fpr1 protein, mouse) RN - 0 (HSH2 protein, mouse) RN - 0 (Lipoxins) RN - 0 (Receptors, Formyl Peptide) RN - 0 (Receptors, Lipoxin) RN - 0 (lipoxin A4) RN - E0399OZS9N (Cyclic AMP) SB - IM MH - Adaptor Proteins, Signal Transducing MH - Animals MH - CHO Cells MH - Cricetinae MH - Cricetulus MH - Cyclic AMP/antagonists & inhibitors/metabolism MH - *Gene Expression Regulation MH - HEK293 Cells MH - Humans MH - Lipoxins/metabolism/*physiology MH - Mice MH - Receptors, Formyl Peptide/*administration & dosage/biosynthesis/*metabolism/physiology MH - Receptors, Lipoxin/biosynthesis/*metabolism EDAT- 2013/05/07 06:00 MHDA- 2013/08/10 06:00 CRDT- 2013/05/07 06:00 PHST- 2013/02/13 00:00 [received] PHST- 2013/04/18 00:00 [revised] PHST- 2013/04/23 00:00 [accepted] PHST- 2013/05/07 06:00 [entrez] PHST- 2013/05/07 06:00 [pubmed] PHST- 2013/08/10 06:00 [medline] AID - S0006-2952(13)00261-X [pii] AID - 10.1016/j.bcp.2013.04.019 [doi] PST - ppublish SO - Biochem Pharmacol. 2013 Jun 15;85(12):1795-802. doi: 10.1016/j.bcp.2013.04.019. Epub 2013 May 1.