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Published ahead of print on October 16, 2003, doi:10.1164/rccm.200207-740OC
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American Journal of Respiratory and Critical Care Medicine Vol 169. pp. 195-200, (2004)
© 2004 American Thoracic Society

Antiinflammatory Roles of Peroxisome Proliferator–activated Receptor {gamma} in Human Alveolar Macrophages

Kazuhiro Asada, Shigekazu Sasaki, Takafumi Suda, Kingo Chida and Hirotoshi Nakamura

Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

Correspondence and requests for reprints should be addressed to Takafumi Suda, M.D., Ph.D., 1-20-1 Handayama, Hamamatsu, 431-3192, Japan. E-mail: suda{at}hama-med.ac.jp

Peroxisome proliferator–activated receptor {gamma} (PPAR{gamma}) is a ligand-activated transcriptional factor belonging to the nuclear receptor superfamily. PPAR{gamma}, which is predominantly expressed in adipose tissue, plays a major regulatory role in glucose metabolism and adipogenesis. Interestingly, recent studies have demonstrated PPAR{gamma} expression in monocytes/macrophages and its antiinflammatory activities. However, it is unclear whether alveolar macrophages (AMs) express functional PPAR{gamma}. The present study was conducted to investigate the expression of PPAR{gamma} by AMs and to elucidate its functional role. Using reverse transcription–polymerase chain reaction and Western blotting, we demonstrated the strong expression of PPARs messenger RNA and protein in freshly isolated human AMs. Ligands of PPAR{gamma}, 15-deoxy-{Delta}12,14prostaglandin J2, and troglitazone significantly decreased LPS-induced tumor necrosis factor-{alpha} 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 PPAR{gamma} expressed by AMs play an antiinflammatory 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 PPAR{gamma} ligands in inflammatory disorders of the lung.

Key Words: peroxisome proliferator–activated receptor {gamma} • alveolar macrophage • tumor necrosis factor-{alpha} • CD36 • phagocytosis




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