Respiratory mucous glycoprotein (MGP) is an essential secretion of airways. The control of these secretions has important implications for many disease states too much or too little MGP can be associated with disease. Dexamethasone is often administered to patients with pulmonary disorders: its effects on MGP have not been clearly delineated. The effect of Dexamethasone on feline respiratory mucous glycoprotein (MGP) secretion in vitro and Dexamethasone's effect correlated with the production of lipomodulin and with the inhibition of production of arachidonic acid metabolites. Dexamethasone caused a dose-dependent, reversible inhibition of MGP secretion, as well as up to a 220% increase in tissue lipomodulin content. This increase in lipomodulin content was associated with a marked reduction in the formation of the arachidonic acid metabolite PGE. The addition of a mouse monoclonal antibody against lipo-modulin completely blocked the Dexamethasone-induced suppression of MGP secretion. The role of eicosanoids in baseline MGP secretion is also being studied by the evaluation of the effect of the lipoxygenase and the cyclooxygenase pathway antagonist eicosatetraynoic acid (ETYA) and the lipoxygenase pathway blocker nordihydroysiairetic acid (NDGA) on MGP secretion. These studies indicate that Dexamethasone inhibits MGP secretion from airways and that this effect is mediated by the induction of lipomodulin formation with resultant inhibition of phospholipase A2. A manuscript is submitted.
