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


Dr H. Takizawa, Department of Medicine and Physical Therapy, University of Tokyo, School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan


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 upregulaled by inflammatory products in the airways.