Abstract
Arachidonic acid metabolites, prostanoids and leukotrienes, are important mediators in airway inflammation. Over the last decade, selective receptors of these mediators have been identified, and the biological functions of these receptors have been clarified in detail. Prostaglandin (PG)D2, thromboxane A2, and cysteinyl leukotrienes may augment allergic inflammation. On the contrary, PGE2, PGI2, and lipoxins may be potent anti-inflammatory mediators involved in airway inflammation.
PGE2 receptors are characterized into four subtypes: EP1, EP2, EP3, and EP4. In our study, EP agonists inhibited mucus secretion and IL-8 release from cultured human airway epithelial cells in vitro. An in vivo study revealed that mucus production and neutrophil or eosinophil infiltration caused by LPS stimulation or allergic inflammation were inhibited by the subcutaneous injection of EP agonists in rat nasal epithelium. These results indicate that PGE2 acts as an anti-inflammatory mediator via EP receptors, and that EP agonists may constitute a new therapeutic strategy.
In this article, recent knowledge of prostanoid and leukotriene functions in the pathogenesis of airway inflammation is reviewed. Their selective receptors and synthetic enzymes may provide novel targets for future drugs.
