Increased expression of endothelin in bronchial epithelial cells of asthmatic patients and effect of corticosteroids.

We have previously demonstrated that human bronchial smooth muscle cells possess specific binding sites for the potent bronchoconstrictive peptide endothelin 1 and that primary cultures of human bronchial epithelial cells constitutively produce an endothelin-like material that binds to smooth muscle cell receptors with a kinetic ability analogous to that shown by the authentic peptide. To evaluate the potential role of airway epithelium-derived endothelin in the pathogenesis of asthma, we have examined here the expression of endothelin in the bronchial epithelial cells of 6 patients with symptomatic asthma and reversible airflow obstruction. The epithelial cells of 5 normal volunteers and 5 patients with chronic bronchitis and airflow obstruction unaffected by bronchodilators were tested as controls. The bronchial epithelial cells of all the asthmatic patients expressed preproendothelin 1 mRNA, as assessed by in situ hybridization, and released high amounts of mature and biologically active endothelin during a 48-h period of incubation (radioimmunoassay). By contrast, the epithelial cells from normal donors did not contain preproendothelin 1 transcripts, and the endothelin-like material in their supernatants was invariably below the detection limit of the assay. Only a few cells from 2 patients with chronic bronchitis expressed preproendothelin mRNA and endothelin immunoreactivity. When hydrocortisone (10(-6)M) was added to the culture medium of asthmatic bronchial epithelial cells for 48 h, the release of immunoreactive endothelin significantly decreased (p < 0.025), but the numbers of cells expressing preproendothelin 1 mRNA did not change to the same extent.