Pleiotropic effect of the proton pump inhibitor esomeprazole leading to suppression of lung inflammation and fibrosis

• DOI: 10.1186/s12967-015-0614-x
• Publication Date: 2015-07-31T10:42:50Z
• Authors: Yohannes T Ghebre...; John P Cooke; William Gerhart; Carol Griego; Jeremy B Brower; Melanie Doyle-Eisele; Benjamin C Moeller; Qingtao Zhou; Lawrence Ho; Joao de Andrade; Ganesh Raghu; Leif Peterson; Andreana Rivera; Glenn D Rosen
• Keywords: Esomeprazole

The beneficial outcome associated with the use of proton pump inhibitors (PPIs) in idiopathic pulmonary fibrosis (IPF) has been reported retrospective studies. To date, no prospective study conducted to confirm these outcomes. In addition, potential mechanism by which PPIs improve measures lung function and/or transplant-free survival IPF not elucidated.Here, we used biochemical, cell biological and preclinical studies evaluate regulation markers inflammation fibrosis. our vitro studies, exposed primary fibroblasts, epithelial endothelial cells ionizing radiation or bleomycin; stimuli typically induce cultured fibroblasts from patients studied effect esomeprazole on collagen release. Our tested efficacy a rat model bleomycin-induced injury. Furthermore, performed analysis interstitial disease (ILD) databases examine survival.The culture revealed that controls suppressing expression pro-inflammatory molecules including vascular adhesion molecule-1, inducible nitric oxide synthase, tumor necrosis factor-alpha (TNF-α) interleukins (IL-1β IL-6). antioxidant is strong induction stress-inducible cytoprotective protein heme oxygenase-1 (HO1) antifibrotic potent inhibition fibroblast proliferation as well downregulation profibrotic proteins receptors for transforming growth factor β (TGFβ), fibronectin matrix metalloproteinases (MMPs). showed robust mitigating inflammatory fibrotic responses murine acute Finally, two ILD was assess patients. Intriguingly, this data demonstrated had prolonged over (median 3.4 vs 2 years).Overall, indicate possibility may have protective directly modulating process suggest they other clinical utility treatment extra-intestinal diseases characterized phases.