Eicosanoids: mediators and therapeutic targets in fibrotic lung disease.
Fibrosis is a common end-stage sequella of a number of acute and chronic lung diseases. Current concepts of pathogenesis implicate dysregulated interactions between epithelial cells and mesenchymal cells. Although investigative efforts have documented important roles for cytokines and growth factors in the pathogenesis of fibrotic lung diseases, these observations have not as yet been translated into efficacious therapies, and there is a pressing need for new pathogenetic insights and therapeutic approaches for these devastating disorders. Eicosanoids are lipid mediators derived from arachidonic acid, the most studied of which are the prostaglandins and leukotrienes. Although they are primarily known for their roles in asthma, pain, fever and vascular responses, present evidence indicates that eicosanoids exert relevant effects on immune/inflammatory, as well as structural, cells pertinent to fibrogenesis. In general, leukotrienes promote, whereas prostaglandin E(2) opposes, fibrogenic responses. An imbalance of eicosanoids also exists in pulmonary fibrosis, which favours the production of leukotrienes over prostaglandin E(2). This review highlights the role of this imbalance in the evolution of fibrotic lung disease, discusses the mechanisms by which it may arise and considers approaches for therapeutic targeting of eicosanoids in these conditions.
Charbeneau
Ryan P
RP
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0642, USA.
Peters-Golden
Marc
M
D002450:Cell Communication / Q000502:physiology; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism; D015777:Eicosanoids / Q000096:biosynthesis*; D006801:Humans; D015289:Leukotrienes / Q000096:biosynthesis / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology
D015777:Eicosanoids; D015289:Leukotrienes; D015232:Dinoprostone