Endotoxin and pro-inflammatory cytokines stimulate endothelin-1 expression and release by airway epithelial cells

• Published in: Clinical and experimental allergy Vol. 24; no. 4; pp. 330 - 336
• Main Authors: NAKANO, J, TAKIZAWA, H, OHTOSHI, T, SHOJI, S, YAMAGUCHI, M, ISHII, A, YANAGISAWA, M, ITO, K
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell 01.04.1994
• Subjects: Aged; Biological and medical sciences; Bronchi - drug effects; Bronchi - physiology; Cells, Cultured; Chronic obstructive pulmonary disease, asthma; Cycloheximide - pharmacology; Cytokines - pharmacology; Endothelins - biosynthesis; Endothelins - genetics; Endothelins - metabolism; Endotoxins - pharmacology; Epithelium - drug effects; Epithelium - physiology; Female; Gene Expression - drug effects; Humans; In Vitro Techniques; Inflammation - etiology; Inflammation - physiopathology; Interleukin-1 - pharmacology; Lipopolysaccharides - pharmacology; Male; Medical sciences; Middle Aged; Pneumology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tumor Necrosis Factor-alpha - pharmacology; Human; Respiratory disease; Pathogenesis; Cytokine; Bronchus; Endothelin 1; Gene expression; Endotoxin; In vitro; Asthma; Microbial origin; Tumor necrosis factor; Interleukin 1; Epithelial cell; Obstructive pulmonary disease; Release
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.1994.tb00243.x

Endothelin is a potent bronchoconstrictor peptide first identified as a novel vasoconstrictor produced by vascular endothelial cells. Recent reports suggest that airway epithelial cells are also capable of releasing this active peptide. To investigate the regulatory mechanism of endothelin expression, we studied the effects of endotoxin and pro-inflammatory cytokines such as interleukin-1 and tumour necrosis factor on the expression and release of endothelin-1 by airway epithelial cells. Both endotoxin and the cytokines stimulated endothelin-1 release by human bronchial epithelial cells. Northern blot analysis showed increased expression of preproendothelin-1 mRNA by these factors. These results suggested that airway epithelial cells might play a role in the local airway smooth muscle tone through the production of endothelin, which might be upregulated by inflammatory products in the airways.