10.6084/m9.figshare.6446024.v1 Thomas H Sisson Thomas H Sisson Paul J Christensen Paul J Christensen Yo Muraki Yo Muraki Anthony Joseph Dils Anthony Joseph Dils Lauren Chibucos Lauren Chibucos Natalya Subbotina Natalya Subbotina Kimio Tohyama Kimio Tohyama Jeffrey C Horowitz Jeffrey C Horowitz Takanori Matsuo Takanori Matsuo Marc Bailie Marc Bailie Sham Nikam Sham Nikam Masatoshi Hazama Masatoshi Hazama Dataset for: Phosphodiesterase 4 Inhibition Reduces Lung Fibrosis Following Targeted Type II Alveolar Epithelial Cell Injury Wiley 2018 Pulmonary Collagen Epithelium Fibroblast Physiology Systems Biology 2018-07-31 12:55:50 Dataset https://wiley.figshare.com/articles/dataset/Dataset_for_Phosphodiesterase_4_Inhibition_Reduces_Lung_Fibrosis_Following_Targeted_Type_II_Alveolar_Epithelial_Cell_Injury/6446024 Fibrosis of the lung constitutes a major clinical challenge and novel therapies are required to alleviate the associated morbidity and mortality. Investigating the anti-fibrotic efficacy of drugs that are already in clinical practice offers an efficient strategy to identify new therapies. The phosphodiesterase 4 (PDE4) inhibitors, approved for the treatment of chronic obstructive pulmonary disease, harbor therapeutic potential for pulmonary fibrosis by augmenting the activity of endogenous anti-fibrotic mediators that signal through cyclic AMP. In the present study, we tested the efficacy of several PDE4 inhibitors including a novel compound (Compound 1) in a murine model of lung fibrosis that results from a targeted type II alveolar epithelial cell injury. We also compared the anti-fibrotic activity of PDE4 inhibition to the two therapies that are FDA-approved for idiopathic pulmonary fibrosis (pirfenidone and nintedanib). We found that both preventative (day 0-21) and therapeutic (day 11-21) dosing regimens of the PDE4 inhibitors significantly ameliorated the weight loss and lung collagen accumulation that are the sequelae of targeted epithelial cell damage. In a therapeutic protocol, the reduction in lung fibrosis with PDE4 inhibitor administration was equivalent to pirfenidone and nintedanib. Treatment with this class of drugs also resulted in a decrease in plasma surfactant protein D concentration, a reduction in the plasma levels of several chemokines implicated in lung fibrosis, and an in vitro inhibition of fibroblast pro-fibrotic gene expression. These results motivate further investigation of PDE4 inhibition as a treatment for patients with fibrotic lung disease.