Anti-inflammatory roles of peroxisome proliferator-activated receptor in human alveolar macrophages

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcriptional factor belonging to the nuclear receptor superfamily. PPARγ, which is predominantly expressed in adipose tissue, plays a major regulatory role in glucose metabolism and adipogenesis. Interestingly, recent studies have demonstrated PPARγ expression in monocytes/macrophages and its anti-inflammatory activities. However, it is unclear whether alveolar macrophages (AMs) express functional PPARγ. The present study was conducted to investigate the expression of PPARγ by AMs and to elucidate its functional role. Using RT-PCR and western blotting, we demonstrated the strong expression of PPARs mRNA and protein in freshly isolated human AMs. Ligands of PPARγ, 15-deoxy-∆ 12,14 prostaglandin J 2 (15d-PGJ 2) and troglitazone, significantly decreased LPS-induced TNF-α production by AMs. These ligands markedly upregulated the expression of CD36, a scavenger receptor that mediates the phagocytosis of apoptotic neutrophils. Indeed, ligand-treated AMs ingested a significantly higher number of apoptotic neutrophils than untreated AMs. These data indicate that PPARγ expressed by AMs play an anti-inflammatory role through inhibiting cytokine production and increasing their CD36 expression together with the enhanced phagocytosis of apoptotic neutrophils, which is an essential process for the resolution of inflammation. This suggests the potential therapeutic application of PPARγ ligands in inflammatory disorders of the lung.