Constitutive expression of endothelin in bronchial epithelial cells of patients with symptomatic and asymptomatic asthma and modulation by histamine and interleukin-1.

摘要

BACKGROUND: An upregulation of endothelin-1 expression occurs in bronchial epithelial cells of asthmatic patients. This peptide may mediate bronchoconstriction in asthma, but the mechanisms that modulate endothelin-I synthesis and release are unknown. OBJECTIVE: This study was done to compare the pattern of endothelin-1 expression in patients with symptomatic and asymptomatic asthma and evaluate the ability of inflammatory factors to upregulate endothelin-1 synthesis and release in the epithelial cells of subjects who are free of symptoms. METHODS: Two groups of 10 asthmatic patients were selected. One group had symptomatic asthma with airflow obstruction and moderately to severely increased airway responsiveness. The second group was free of symptoms: they did not show airflow obstruction, and airway responsiveness was borderline or slightly increased. Bronchial biopsy specimens were obtained by means of bronchoscopy and used for immunohistochemical evaluation, epithelial cell isolation, and stimulation experiments with interleukin-1 and histamine. RESULTS: Endothelin-1 immunoreactivity was detected in vivo in the bronchial epithelial cells of all the patients with symptoms and in only two subjects without current symptoms. Incubation of bronchial epithelial cells from patients with asymptomatic asthma with interleukin-1 or histamine, for 8 to 24 hours, resulted in increased expression of endothelin-1 messenger RNA and release of appreciable amounts of the peptide to the culture medium. Those effects were dose- and time-dependent. Histamine and interleukin-1 were effective at concentrations similar to those detected in the bronchoalveolar lavage of patients with symptomatic asthma. CONCLUSION: Endothelin-expression is upregulated in bronchial epithelial cells of asthmatic patients with symptoms and evidence of functional derangement as compared with patients without symptoms and airflow obstruction. Exposure of cells from patients with asymptomatic asthma to factors that are released during acuteexacerbation of the disease induces endothelin synthesis and release.