TY - JOUR
T1 - Elevated Expression of Endothelin-1 and Endothelin-converting Enzyme-1 in Idiopathic Pulmonary Fibrosis
T2 - Possible Involvement of Proinflammatory Cytokines
AU - Saleh, Dina
AU - Furukawa, Kanako
AU - Tsao, Ming Sound
AU - Maghazachi, Azzam
AU - Corrin, Bryan
AU - Yanagisawa, Masashi
AU - Barnes, Peter J.
AU - Giaid, Adel
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
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U2 - 10.1165/ajrcmb.16.2.9032126
DO - 10.1165/ajrcmb.16.2.9032126
M3 - Article
C2 - 9032126
AN - SCOPUS:0031065214
SN - 1044-1549
VL - 16
SP - 187
EP - 193
JO - American journal of respiratory cell and molecular biology
JF - American journal of respiratory cell and molecular biology
IS - 2
ER -