PT - JOURNAL ARTICLE AU - Simon Lea AU - Jonathan Plumb AU - Hannah Metcalfe AU - Dianne Spicer AU - Paul Woodman AU - J. Craig Fox AU - Dave Singh TI - The effect of peroxisome proliferator-activated receptor-γ ligands on <em>in vitro</em> and <em>in vivo</em> models of COPD AID - 10.1183/09031936.00187812 DP - 2014 Feb 01 TA - European Respiratory Journal PG - 409--420 VI - 43 IP - 2 4099 - http://erj.ersjournals.com/content/43/2/409.short 4100 - http://erj.ersjournals.com/content/43/2/409.full SO - Eur Respir J2014 Feb 01; 43 AB - Peroxisome proliferator-activated receptor (PPAR)-γ is expressed in alveolar macrophages. The anti-inflammatory potential of the PPAR-γ 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-γ 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-γ ligands and corticosteroids on lipopolysaccharide-induced cytokine production, alternative macrophage activation (M2) gene expression and efferocytosis. The effects of PPAR-γ ligands in a subchronic tobacco smoke model in mice were investigated. PPAR-γ 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-γ ligands reduced tumour necrosis factor-α 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-γ agonists on corticosteroid-resistant disease, tobacco smoke-induced pulmonary inflammation, skewing of macrophage phenotype and clearance of apoptotic neutrophils. Biological actions of a PPAR-γ agonist shown in COPD-relevant models may affect progression and side-effects in patients http://ow.ly/r50DF