Elevated expression of endothelin-1 and endothelin-converting enzyme-1 in idiopathic pulmonary fibrosis: possible involvement of proinflammatory cytokines.

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 br...