Control of phospholipase A2 activities for the treatment of inflammatory conditions.
Phospholipase-A2 (PLA2) enzymes hydrolyze cell membrane phospholipids to produce arachidonic acid (AA) and lyso-phospholipids (LysoPL), playing a key role in the production of inflammatory lipid mediators, mainly eicosanoids. They are therefore considered pro-inflammatory enzymes and their inhibition has long been recognized as a desirable therapeutic target. However, attempts to develop suitable PLA2 inhibitors for the treatment of inflammatory diseases have yet to succeed. This is due to their functional and structural diversity, and their homeostatic and even anti-inflammatory roles in certain circumstances. In the present review we outline the diversity and functions of PLA2 isoforms, and their interplay in the induction and inhibition of inflammatory processes, with emphasis on discussing approaches for therapeutic manipulation of PLA2 activities.
Yedgar
Saul
S
Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel. yedgar@md.huji.ac.il
Cohen
Yuval
Y
Shoseyov
David
D
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000201:enzymology*; D008246:Lysophospholipids; D008563:Membrane Lipids / Q000378:metabolism; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054467:Phospholipases A2
D015777:Eicosanoids; D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D008563:Membrane Lipids; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2