ENDOTOXIN AND PRO-INFLAMMATORY CYTOKINES STIMULATE ENDOTHELIN-1 EXPRESSION AND RELEASE BY AIRWAY EPITHELIAL-CELLS

Endothelin is a potent bronchoconstrictor peptide first identified as a novel vasoconstricter produced by vascular endothelial cells. Recent reports suggest that airway epithelial cells are also capable of rele asing this active peptide. To investigate the regulatory mechanism of endothelin expression, we studied the effects of endotoxin and pro-inf lammatory cytokines such as interleukin-1 and tumour necrosis factor o n the expression and release of endothelin-1 by airway epithelial cell s. Both endotoxin and the cytokines stimulated endothelin-1 release by human bronchial epithelial cells. Northern blot analysis showed incre ased expression of preproendothelin-1 mRNA by these factors. These res ults suggested that airway epithelial cells might play a role in the l ocal airway smooth muscle tone through the production of endothelin, w hich might be upregulated by inflammatory products in the airways.