Elevated Expression of Endothelin-1 and Endothelin-converting Enzyme-1 in Idiopathic Pulmonary Fibrosis: Possible Involvement of Proinflammatory Cytokines

Dina Saleh, Kanako Furukawa, Ming Sound Tsao, Azzam Maghazachi, Bryan Corrin, Masashi Yanagisawa, Peter J. Barnes, Adel Giaid

Research output: Contribution to journalArticle

141 Scopus citations

Abstract

Endothelin-1 (ET-1) is a vasoconstrictor, bronchoconstrictor, and mitogenic peptide which is enzymatically converted from a biologically inactive big ET to mature ET (21 amino acid) by the ET-converting enzyme (ECE). Here, we investigate the expression of ECE-1, big ET-1, and ET-1 in the lungs of patients with idiopathic pulmonary fibrosis (IPF) and compare it to those of normal subjects using immunohistochemistry and in situ hybridization. In normal lungs, focal moderate expression of all three molecules is localized to airway epithelium, pulmonary endothelium, and airway and vascular smooth muscle cells. Serous bronchial glands also expressed ET-1 and ECE-1. In IPF, strong diffuse expression of ECE-1 was seen in airway epithelium, proliferating type II pneumocytes, and in endothelial and inflammatory cells. ECE-1 immunostaining was colocalized to big ET-1 and ET-1 immunostaining, and correlated with disease activity (P < 0.05). To study regulatory mechanisms of ET-1 and ECE-1 expression, human normal bronchial epithelial (NBE) cells were treated with cytokines and analyzed by radioimmunoassay and Northern blot. Incubation of human NBE cells with IL-1α and -β or tumor necrosis factor α (TNFα) resulted in a significant increase in ET-1 release and mRNA expression. TNFα resulted in a significant increase in ECE-1 mRNA expression. These findings demonstrated the colocalization of the precursor and active ET-1, and ECE-1 in the same cell, and that ECE-1 expression is elevated in IPF. In addition, increased expression of ET-1 and ECE-1 in IPF may be mediated by proinflammatory cytokines.

Original languageEnglish (US)
Pages (from-to)187-193
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume16
Issue number2
DOIs
StatePublished - Jan 1 1997

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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