The effect of peroxisome proliferator-activated receptor-γ ligands on in vitro and in vivo models of COPD.
Eur Respir J
; 43(2): 409-20, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-23794466
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Macrófagos Alveolares
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Doença Pulmonar Obstrutiva Crônica
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PPAR gama
Tipo de estudo:
Prognostic_studies
Limite:
Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article