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Accueil Olodaterol Shows Anti-Fibrotic Efficacy in in vitro and in vivo Models of Pulmonary Fibrosis.
Olodaterol Shows Anti-Fibrotic Efficacy in in vitro and in vivo Models of Pulmonary Fibrosis. Imprimer Envoyer
Samedi, 19 Août 2017 07:07
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Olodaterol Shows Anti-Fibrotic Efficacy in in vitro and in vivo Models of Pulmonary Fibrosis.

Br J Pharmacol. 2017 Aug 15;:

Authors: Herrmann FE, Wollin L, Wirth J, Gantner F, Lämmle B, Wex E

Abstract
BACKGROUND AND PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease characterized by excessive fibroblast activation ultimately leading to scarring of the lungs. Although, the activation of β2 -adrenergic receptors (β2 -AR) has been shown to inhibit pro-fibrotic events primarily in cell lines, the role of β2 -AR agonism has not yet been fully characterized. The aim of our study was to explore the anti-fibrotic activity of the long-acting β2 -AR-agonist olodaterol in primary human lung fibroblasts, and in murine models of pulmonary fibrosis.
EXPERIMENTAL APPROACH: We assessed the activity of olodaterol to inhibit various pro-fibrotic mechanisms, induced by different pro-fibrotic mediators, in primary human lung fibroblasts from control donors (HLF) and patients with IPF (IPF-LF). The in vivo anti-fibrotic activity of olodaterol, given once-daily by inhalation in either a preventive or therapeutic treatment regimen, was explored in murine models of lung fibrosis induced by either bleomycin or the overexpression of TGF-β1.
KEY RESULTS: In both, HLF and IPF-LF, olodaterol attenuated TGF-β-induced expression of α-smooth muscle actin, fibronectin and endothelin-1 (ET-1), FGF- and PDGF-induced motility and proliferation, and TGF-β/ET-1-induced contraction. In vivo olodaterol significantly attenuated the bleomycin-induced increase in lung weight, reduced bronchoalveolar lavage cell counts, inhibited pro-fibrotic mediator release (TGF-ß, MMP-9, TIMP-1) and increased the forced vital capacity, though only with the preventive treatment regimen. In the TGF-β-overexpressing model, olodaterol additionally reduced the Col3A1 mRNA expression.
CONCLUSION AND IMPLICATIONS: In conclusion, olodaterol showed anti-fibrotic properties in primary human lung fibroblasts from control and IPF patients and in murine models of lung fibrosis.

PMID: 28810065 [PubMed - as supplied by publisher]


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Accueil Olodaterol Shows Anti-Fibrotic Efficacy in in vitro and in vivo Models of Pulmonary Fibrosis. Top