Antiinflammatory roles of peroxisome proliferator-activated receptor gamma in human alveolar macrophages.
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcriptional factor belonging to the nuclear receptor superfamily. PPARgamma, which is predominantly expressed in adipose tissue, plays a major regulatory role in glucose metabolism and adipogenesis. Interestingly, recent studies have demonstrated PPARgamma expression in monocytes/macrophages and its antiinflammatory activities. However, it is unclear whether alveolar macrophages (AMs) express functional PPARgamma. The present study was conducted to investigate the expression of PPARgamma 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 PPARgamma, 15-deoxy-delta(12,14)prostaglandin 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 PPARgamma 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 PPARgamma ligands in inflammatory disorders of the lung.
Asada
Kazuhiro
K
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Sasaki
Shigekazu
S
Suda
Takafumi
T
Chida
Kingo
K
Nakamura
Hirotoshi
H
D017209:Apoptosis; D018955:CD36 Antigens / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D010587:Phagocytosis; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism / Q000502:physiology*; D045162:Thiazolidinediones / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D000077288:Troglitazone; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D018955:CD36 Antigens; D002839:Chromans; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000077288:Troglitazone; D015230:Prostaglandin D2