Abstract
Background: Endothelin-1 (ET-1) has a considerable fibrogenic activity and it has been implicated in the pathogenesis of pulmonary fibrosis. Increased levels of ET-1 have been demonstrated in serum and bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis (IPF), and lung tissue of IPF patients show increased ET-1 immunoreactivity. The biological effects of ET-1 are mediated through two receptors – ET-A and ET-B. However, disease specific patterns of ET receptor expression in fibrotic and normal primary human lung fibroblasts had not been studied yet.
Methods: Primary human lung fibroblasts were isolated and propagated from lung parenchyma derived from patients with IPF (n=4) as well as from parenchyma derived from healthy controls (n=4). Isolated cells were grown to confluence. After transforming growth factor beta1 (TGF-beta1) stimulation total protein was harvested and immuno blot analysis was performed.
Results: In fibroblasts derived from patients with IPF the ET-A and ET-B receptors were equally expressed, whereas in control fibroblasts expression of both receptors was lower compared to IPF cells. Stimulation with TGF-beta1 caused a further increase of ET-A and ET-B receptor expression by IPF fibroblasts, but no such up-regulation was detected in control fibroblasts.
Conclusion: Our data demonstrate for the first time a difference in the pattern of ET receptor expression between IPF and normal lung, and a disease-specific reaction upon stimulation with TGF-beta1. Our observations may have implications for our understanding of the roles of ET-1 and TGF-beta1 in the pathogenesis of IPF.
- © 2011 ERS