Is iPLA₂β a Novel Target for the Development of New Strategies to Alleviate Inflammatory Bowel Disease?

Excerpt

Phospholipases A₂ (PLA₂s), lipolytic enzymes that release fatty acids (FAs) and lysophospholipids from the hydrolysis of the sn-2 ester bond of membrane glycerophospholipids, modulate (phospho)lipid-related homeostatic and stimulus-induced intracellular processes, linking lipid metabolism with cell signaling [1, 2]. Although the diverse products released by their activity on cell membranes have signaling and metabolic activities in and of themselves, the products may be further converted into hundreds of lipid mediator molecules, including arachidonic acid (AA)-derived eicosanoids and ω-3 polyunsaturated FA-derived pro-resolving mediators [3]. Unsurprisingly, PLA₂s are involved in diverse and fundamental biological processes, including inflammation, immunity, reproduction, atherosclerosis, cancer, and neurodegeneration [2]. Among the human PLA₂s, eleven members belong to the secreted PLA₂ (sPLA₂) family of low-molecular-mass Ca²⁺-dependent enzymes that function in the extracellular space on cell membranes, lipoproteins, bacteria, microparticles, and viruses [3, 4]. Most PLA₂s are, however, intracellular enzymes, including the Ca²⁺-dependent cytosolic PLA₂s (cPLA₂s or group IV PLA₂s) and the Ca²⁺-independent PLA₂s (iPLA₂s or group VI PLA₂s). Among the nine enzymes within the iPLA₂ family, also named the patatin-like phospholipase domain-containing lipase (PNPLA) family, iPLA₂β (also PNPLA9 or group VIA PLA₂) is far and away the most studied enzyme [5]. …