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 this study was to analyze the synthesis of ET-1 in human airway epithelial cells and macrophages under basal conditions and after challenge with 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 U937. At baseline, U937 cells released low amounts of ET-1 peptide, whereas ET-1 was not detectable in BEAS-2B cells. After TNF alpha treatment, BEAS-2B cells, but not U937 cells, showed a significant increase in ET-1 expression, both at the mRNA and peptide levels. In contrast, dexamethasone elicited an increased amount of ET-1 peptide in U937 medium, but not in BEAS-2B cells. In this latter cell line, dexamethasone pretreatment 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 induction and inhibition in local microenvironments.
Aubert
J D
JD
Départment de Médicine, BH-07 CHUV, CH-1011 Lausanne, Switzerland. john-David.Aubert@chuv.hospvd.ch
Juillerat-Jeanneret
L
L
Leuenberger
P
P
D015152:Blotting, Northern; D001980:Bronchi / Q000378:metabolism*; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D019332:Endothelin-1 / Q000096:biosynthesis*; D016232:Endothelins / Q000235:genetics; D006801:Humans; D009000:Monocytes / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone