Role of formyl peptide receptor 2 (FPR2) in the normal brain and in neurological conditions

Wei Yi Ong; John Jia En Chua

doi:10.4103/1673-5374.262575

摘要：There is much recent interest in the role of the anti-inflamma-tory molecules and their receptors in the normal brain and in neurological disorders. The formyl peptide receptor (FPR) sub-family of G protein-coupled receptors play important roles in these processes. Binding to specific peptides triggers activation of FPRs, leading to signalling events that regulate inflammatory responses. One member of this subfamily of receptors is FPR2, also known as ALX (the lipoxin A4 (LXA4) receptor). FPR2 is specifically activated by LXA4 and resolvin D1 (RvD1) (Pi-rault and B?ck, 2018). LXA4 is an anti-inflammatory molecule produced by the action of lipoxygenases on arachidonic acid, while RvD1 is produced by the action of lipoxygenases on do-cosahexaenoic acid, a component of fish oil. Activation of FPR2 by LXA4 or RvD1 triggers downstream signalling cascades, e.g., inhibition of calcium-calmodulin dependent protein kinase and p38 mitogen-activated protein kinase phosphorylation, leading to a reduction in inflammatory responses. Annexin A1 (ANXA1) is another molecule which could interact with FPR2. A Ca2+-dependent phospholipid-binding protein, ANXA1 sup-presses phospholipase A2 activity to reduce arachidonic acid and eicosanoid production and decrease leukocyte inflammato-ry events such as cell migration, chemotaxis, phagocytosis and respiratory burst. While many studies have shown that binding to FPR2 is a chemotactic signal to attract macrophages to the site of tissue injury, other studies have highlighted that it is part of an anti-inflammatory process. For example, from some of the studies detailed below (summarized in Figure 1), it seems that activation of this receptor does not itself cause further produc-tion of pro-inflammatory mediators by macrophages. Instead, FPR2 appears to attract macrophages and other immune cells to the site of tissue injury to initiate a "quiet mopping-up process"