Endothelin-1 in idiopathic pulmonary fibrosis.

Abstract

Aims-To evaluate whether endothelin-1 is involved in the pathology of idiopathic pulmonary fibrosis (IPF). Methods-Plasma endothelin-1 concentrations were evaluated in 37 patients with IPF and 27 normal controls by radioimmunoassay. In addition, expression of endothelin-1 in lung tissue was evaluated in biopsy specimens obtained from four patients with IPF. Three biopsy specimens of normal lung were used as controls. Endothelin-1 immunoreactivity was detected using immunohistochemistry. Results-Elevated endothelin-l plasma concentrations were found in patients with IPF compared with controls and a positive correlation was found with duration ofdisease. No significant difference was observed between treated and untreated patients with IPF. Increased endothelin-1 immunoreactivity was found in lungs of three of four patients with IPF. Endothelin-l positive cells consisted mainly of small vessel endothelial cells. Some scattered macrophages were also positive. Conclusions-Elevated plasma concentrations and expression of endothelin-1 in lung tissue are suggestive of increased production of endothelin-1 in at least a proportion of patients with IPF. Consequently, endothelin-l activity could play a role in the fibrogenic process of the disease. (J7 Clin Pathol 1995;48:330-334)

Involvement of endothelin in graft-versus-host disease after rat small bowel transplantation

“…We observed a marked thickening of the alveolar wall and a corresponding reduction in ET-1 staining intensity after the peak increase in ET-1 levels in tissue extracts. Uguccioni et al reported that ET-1 might play a role in the fibrogenic process of idiopathic pulmonary fibrosis (IPF) [14]. The histological evidence of IPF resembles the pulmonary lesions observed in this study, thus suggesting the fibrogenic process of ET-1 in the course of GVHD.…”

A Pathogenetic Role for Endothelin-1 in Peritoneal Dialysis-Associated Fibrosis

“…28,29 ET-1 is normally produced by endothelial cells, but it has been shown also to be overexpressed by fibroblasts in certain fibrotic conditions, including scleroderma and idiopathic pulmonary fibrosis. 30 Recent reports, including our own work, have shown that ET-1 expression is highly induced by TGF-b1 stimulation, and like TGF-b1, ET-1 has been described to promote the epithelial-to-mesenchymal transition.…”

Blocking endothelin: breaking new ground

“…There is now substantial evidence to support the notion that ET has mitogenic effects on fibroblasts, reduces collagen breakdown and induces the synthesis of ECM components, all contributing to fibrosis [10]. ET has been detected in the plasma of patients with IPF at significantly higher levels compared with matched controls (p,0.01) [11] and in patients with scleroderma, levels of ET in bronchoalveolar lavage fluid are higher in patients with lung fibrosis than in patients without lung involvement ( fig. 4) [12].…”