Modulation of endothelin production and metabolism in guinea pig cultured tracheal epithelial cells

Abstract

Endothelins (ET-1, ET-2, ET-3) are potent bronchoconstrictors and growth-promoting mediators. ET-1 is released from various cells such as endothelial and epithelial cells. In patients with Status Asthmaticus and other pulmonary disorders, the expression and production of ET-1 are increased. Treatment of asthmatics with corticosteroids and salbutamol reduce the content of ir-ETs in the bronchoalveolar lavage fluid. In the present study, the pathway of ET biosynthesis and metabolism in guinea-pig tracheal epithelial cells, and the effects of cytokines and asthma drugs, dexamethasone (DEX) and salbutamol, on ET production were investigated. Data suggest that ET-1 is simultaneously produced and degraded by guinea-pig tracheal epithelial cells via phosphoramidon-sensitive ECE and NEP pathways, respectively. Pro-inflammatory cytokines stimulated ET production. DEX and salbutamol decreased ET-1 release, this could be one of the beneficial effects of corticosteroids and [bêta]2-agonists in asthma therapy. Forskolin and 8-bromo-cAMP reduced basal lipopolysaccharide-induced release of ir-ETs, suggesting a cAMP-dependent down-regulation of ET-1 production in guinea-pig tracheal epithelial cells"--Résumé abrégé par UMI