EXPRESSION OF ENDOTHELIN-1 IN HUMAN BRONCHO-EPITHELIAL AND MONOCYTIC CELL-LINES - INFLUENCE OF TUMOR-NECROSIS-FACTOR-ALPHA AND DEXAMETHASONE

Abnormal endothelin-1 (ET-1) expression has been observed in bronchial asthma and systemic sclerosis with lung involvement. The purpose of t his study was to analyze the synthesis of ET-1 in human airway epithel ial cells and macrophages under basal conditions and after challenge w ith tumor necrosis factor-alpha (TNF alpha) or with the glucocorticoid dexamethasone. The ET-1 mRNA level and peptide release were measured in the broncho-epithelial cells BEAS-2B and the monocytic cell line U9 37. At baseline, U937 cells released low amounts of ET-1 peptide, wher eas ET-1 was not detectable in BEAS-2B cells. After TNF alpha treatmen t, BEAS-2B cells, but not U937 cells, showed a significant increase in ET-1 expression, both at the mRNA and peptide levels. In contrast, de xamethasone elicited an increased amount of ET-1 peptide in U937 mediu m, but not in BEAS-2B cells. In this latter cell line, dexamethasone p retreatment was unable to inhibit the TNF alpha-induced expression. We conclude that response to TNF alpha and glucocorticoids is cell-type specific with respect to ET-1 production. The response of lung tissue to these agents in vivo is likely to be the overall balance of inducti on and inhibition in local microenvironments. (C) 1997 Elsevier Scienc e Inc.