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Prostanoids are important endogenous signalling molecules that are produced locally both physiologically and in inflammatory diseases and have potent effects on a number of inflammatory processes. Endogenous prostaglandin production consists of several stages: conversion of membrane phospholipid to arachidonic acid via phospholipase A2, conversion of arachidonic acid to PGG2 by cyclo-oxygenase (COX), a peroxidase reaction to produce PGH2 and then conversion of PGH2 by specific synthases and isomerases to PGE2, PGI2, PGF2α or PGD2. COX is present in most cells, and it is the synthase/isomerase complement of the cell that determines the balance of prostanoids produced by a given cell type. Inflammatory cells tend to produce PGD2 and PGF2α, whereas airway structural cells such as smooth muscle (airway and vascular), fibroblasts, endothelial and epithelial cells produce an abundance of PGE2 or PGI2.1
In contrast to PGD2 and PGF2α, which are predominantly pro-inflammatory, PGE2 is predominantly anti-inflammatory.2 PGE2 inhibits acetylcholine release from parasympathetic nerve endings, mast cell mediator release and cellular responses in eosinophils, macrophages …