title: Increased expression of endothelin in bronchial epithelial cells of asthmatic patients and effect of corticosteroids.
abstract: 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.
authors.affiliation: Diagnostic Center for Respiratory and Allergic Diseases, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Vittori
authors.forename: M
authors.initials: M
authors.lastname: Marini
authors.forename: A
authors.initials: A
authors.lastname: Fasoli
authors.forename: R
authors.initials: R
authors.lastname: De Franchis
authors.forename: S
authors.initials: S
authors.lastname: Mattoli
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D001706:Biopsy; D001980:Bronchi / Q000473:pathology*; D001999:Bronchoscopy; D019332:Endothelin-1; D016232:Endothelins / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D004848:Epithelium / Q000473:pathology; D005069:Evaluation Studies as Topic; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D010366:Peak Expiratory Flow Rate; D011498:Protein Precursors / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
chemical_list: D000305:Adrenal Cortex Hormones; D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors