@article {HerrmannP878, author = {Franziska Herrmann and Lutz Wollin and Eva Wex}, title = {Late-breaking abstract: Olodaterol inhibits pro-fibrotic mechanisms in primary human lung fibroblasts}, volume = {44}, number = {Suppl 58}, elocation-id = {P878}, year = {2014}, publisher = {European Respiratory Society}, abstract = {Background: Pro-fibrotic activity of lung fibroblasts results in airway remodeling observed in COPD. β2-agonists were shown to inhibit fibrotic events including fibroblast proliferation and extracellular matrix synthesis. However, these effects were mainly shown in cell lines but not in primary human lung fibroblasts.Aim: To test the efficacy of the long-acting β2-agonist (LABA) olodaterol to inhibit pro-fibrotic events in primary human lung fibroblasts (HLFs).Methods: HLFs were pre-treated with olodaterol for 30 min and subsequently stimulated with pro-fibrotic mediators (TGF-β, PDGF, FGF) in the presence of olodaterol. Transformation, migration or proliferation assays were performed for 48, 72 or 90 h, respectively. Alpha-smooth muscle actin (α-SMA) expression was measured by FACS analysis, proliferation was determined by BrdU incorporation and cell motility was determined by time lapse microscopy and manual single cell tracking.Results: Functionality of the β2-receptor on HLFs was determined measuring olodaterol-induced cAMP release. Olodaterol concentration-dependently induced cAMP with an IC50 of 200 pM. Stimulation of primary HLFs with TGF-β-induced α-SMA expression and stimulation with both, PDGF and FGF, induced fibroblast proliferation and motility. TGF-β-induced α-SMA expression was attenuated by olodaterol with an IC50 value of 10 pM and a maximal efficacy of 90 \% at 300 pM. With similar IC50 values olodaterol also reduced PDGF- or FGF-induced proliferation (\~{}50 and 30\% at 1 nM) and motility (\~{}45 and 85\% at 1 nM).Conclusions: Olodaterol attenuates pro-fibrotic events in primary human lung fibroblasts. These data support additional beneficial functions of olodaterol beyond bronchodilation.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/44/Suppl_58/P878}, eprint = {https://erj.ersjournals.com/content}, journal = {European Respiratory Journal} }