The effect of peroxisome proliferatoractivated receptor-c ligands on in vitro and in vivo models of COPD

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Abstract

Peroxisome proliferator-activated receptor (PPAR)-c is expressed in alveolar macrophages. The anti-inflammatory potential of the PPAR-c ligands rosiglitazone and pioglitazone were investigated using in vitro alveolar macrophage models and in vivo animal models relevant to chronic obstructive pulmonary disease (COPD). PPAR-c protein and gene expression in COPD alveolar macrophages was compared with control smokers and never-smokers. COPD macrophages were used to investigate the effects of PPAR-c ligands and corticosteroids on lipopolysaccharide-induced cytokine production, alternative macrophage activation (M2) gene expression and efferocytosis. The effects of PPAR-c ligands in a subchronic tobacco smoke model in mice were investigated. PPAR-c protein expression was similar in COPD patients compared to controls, although increased gene expression levels were observed in COPD patients and control smokers compared to never-smokers. PPAR-c ligands reduced tumour necrosis factor-a and CC chemokine ligand-5, but not CXC chemokine ligand-8, in COPD alveolar macrophages; these effects were generally less than those of the corticosteroid dexamethasone. Rosiglitazone increased M2 gene expression and enhanced efferocytosis of apoptotic neutrophils. Rosiglitazone and pioglitazone attenuated airway neutrophilia in a corticosteroid-resistant mouse model of pulmonary inflammation. We show biological actions of PPAR-c agonists on corticosteroid-resistant disease, tobacco smokeinduced pulmonary inflammation, skewing of macrophage phenotype and clearance of apoptotic neutrophils. Copyright © ERS 2014.

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Lea, S., Plumb, J., Metcalfe, H., Spicer, D., Woodman, P., Fox, J. C., & Singh, D. (2014). The effect of peroxisome proliferatoractivated receptor-c ligands on in vitro and in vivo models of COPD. European Respiratory Journal, 43(2), 409–420. https://doi.org/10.1183/09031936.00187812

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