AIRWAY EPITHELIUM AS AN EFFECTOR OF INFLAMMATION - MOLECULAR REGULATION OF SECONDARY MEDIATORS

Deleterious environmental stimuli cause the airway epithelium to respo nd with increased secretions of mucus, reaction of oxygen/nitrogen spe cies, changes in ciliary beating, and the influx of inflammatory cells , The epithelium is a target for factors released by infiltrating infl ammatory cells, and has recently been shown to serve as an effector of such inflammation, Molecular mechanisms regulating production of seco ndary inflammatory mediators (cytokines, lipid mediators, and reactive oxygen/nitrogen species) have yet to be fully described. This report reviews the production of secondary mediators by epithelial cells and by airway epithelium. Lipid mediators are enzymatically produced by th e airway epithelium in response to primary mediators, Molecular mechan isms regulating the production of cyclo-oxygenase, lipoxygenase and pr ostaglandin synthase are discussed, along with the potential of lipid mediators to produce inflammation, The molecular regulation of nitric oxide production is also described in the context of its role as a sig nalling molecule in pathways regulating secretion of mucus, ciliary mo tion, and intercellular adhesion molecule-1 (ICAM-1) expression, The p roduction of cytokines by the airway epithelium is shown to play a rol e in causing inflammation associated with respiratory diseases, Partic ular attention is paid to molecular mechanisms governing the expressio n of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), a nd interleukin-8 (IL-8).