Functional coupling and differential regulation of the phospholipase A2-cyclooxygenase pathways in inflammation.

摘要: Prostaglandins generated by the phospholipase A2 (PLA2)/cyclooxygenase (COX) pathway are well known to mediate diverse intracellular and extracellular effects that regulate mammalian development, vascular function, renal physiology, parturition, immune responses infection or wounding. In immune-mediated diseases in certain cancers, this is aberrantly up-regulated excessive prostaglandin production contributes pathology. It now there two isoforms of COX multiple secreted PLA2 enzymes. The use isoform-specific inhibitors, coupled with antisense vivo gene deletion experiments, has identified independent pathways arachidonic acid metabolism, which differentially regulated at levels expression, protein phosphorylation, cellular localization. There cross-talk between level substrate supply apparently compartmentalized. Knockout studies have shown play roles immediate delayed agonist-induced synthesis. Cytosolic PLA2-alpha essential for both responses. Inducible forms are, as yet, not either response exception vitro murine mast cell instances macrophage These enzymes amplify likely modulate severity diseases.