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

Am Rev Respir Dis. 1992 Nov;146(5 Pt 1):1320-5. doi: 10.1164/ajrccm/146.5_Pt_1.1320.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / pharmacology
  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Asthma / drug therapy
  • Asthma / genetics
  • Asthma / pathology*
  • Biopsy
  • Bronchi / pathology*
  • Bronchoscopy
  • Endothelin-1
  • Endothelins / chemistry*
  • Endothelins / drug effects
  • Endothelins / metabolism
  • Epithelium / pathology
  • Evaluation Studies as Topic
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Peak Expiratory Flow Rate
  • Protein Precursors / chemistry
  • Protein Precursors / drug effects
  • Protein Precursors / metabolism


  • Adrenal Cortex Hormones
  • Endothelin-1
  • Endothelins
  • Protein Precursors