传出细胞增多
罗格列酮
过氧化物酶体增殖物激活受体
肺泡巨噬细胞
慢性阻塞性肺病
炎症
趋化因子
医学
内科学
内分泌学
肿瘤坏死因子α
免疫学
体内
药理学
巨噬细胞
受体
生物
体外
生物化学
生物技术
作者
Simon Lea,Jonathan Plumb,Hannah J. Metcalfe,Diane Spicer,Paul Woodman,Jayne C Fox,Dave Singh
出处
期刊:The European respiratory journal
[European Respiratory Society]
日期:2013-06-21
卷期号:43 (2): 409-420
被引量:88
标识
DOI:10.1183/09031936.00187812
摘要
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.
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