Identification of new formyl peptide receptor-2 (FPR2) agonists with anti-inflammatory properties

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Joanna Slusarczyk
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Hetal B. Patel ◽  
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2017 ◽  
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Felix Becker ◽  
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Julia C Buckingham ◽  
Felicity N E Gavins

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Antonio Recchiuti

Lipoxins (LXs) represent a class of arachidonic acid (AA) metabolites that carry potent immunoregulatory and anti-inflammatory properties, LXA4and LXB4being the main components of this series. LXs are generated by cooperation between 5-lipoxygenase (LO) and 12- or 15-LO during cell-cell interactions or by single cell types. LX epimers at carbon 15, the 15-epi-LXs, are formed by aspirin-acetylated cyclooxygenase-2 (COX-2) in cooperation with 5-LO. 15-epi-LXA4is also termed aspirin-triggered LX (ATL).In vivostudies with stable LX and ATL analogs have established that these eicosanoids possess potent anti-inflammatory activities. A LXA4receptor has been cloned. It belongs to the family of chemotactic receptors and clusters with formyl peptide receptors on chromosome 19. Therefore, it was initially denominated formyl peptide receptor like 1 (FPRL1). This receptor binds with high affinity and stereoselectivity LXA4and ATL. It also recognizes a variety of peptides, synthetic, endogenously generated, or disease associated, but with lower affinity compared to LXA4. For this reason, this receptor has been renamed ALX. This review summarizes the current knowledge on ALX expression, signaling, and potential pathophysiological role. The involvement of additional recognition sites in LX bioactions is also discussed.


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