A novel pharmacologic action of glucocorticosteroids on leukotriene C-4 catabolism

Leukotriene (LT) C-4, a potent chemical mediator in human bronchial asthma, is metabolized to less active LTE4 via LTD4 in 2 consecutive enzymatic rea ctions by gamma -glutamyl transpeptidases and dipeptidases. We examined whe ther this inactivation process of LTC4 was affected by fluticasone propiona te, beclomethasone dipropionate, disodium cromoglycate, and salbutamol sulf ate in transformed human bronchial epithelial cells. Fluticasone propionate and beclomethasone dipropionate accelerated LTC4 catabolism by inducing ac tivity of a LTC4-degrading enzyme, gamma -glutamyl transpeptidase-related e nzyme (gamma -GTPRE), in transformed human bronchial epithelial cells. The activation of gamma -GTPRE might be regulated transcriptionally. This is a novel regulatory mechanism by which glucocorticosteroids exert antiasthma a ctivities.