Peroxisome proliferator-activated receptor gamma and ligands inhibit surfactant protein B gene expression in the lung.
Pulmonary nonciliated bronchiolar epithelial cells (Clara cells) and alveolar type II (AT II) epithelial cells are responsible for surfactant synthesis and secretion. These cells are highly lipogenic with a high lipid turnover rate. Although only 10% of surfactant lipids are neutral lipids, they play very important roles in maintaining pulmonary surfactant homeostasis. Many metabolic intermediate products of neutral lipids serve as ligands for various nuclear receptors that bind to target genes to influence gene transcription. In this report, the functional role of the neutral lipid metabolites, 15-deoxy-Delta12,14-prostaglandin J2 and 9-hydroxyoctadecanoic acids, and peroxisome proliferator-activated receptor gamma was evaluated in surfactant protein B gene regulation. These reagents down-regulated surfactant protein B gene expression in respiratory epithelial cells at the transcriptional level in both cell line and whole lung explant systems. The studies support the concept that surfactant protein B homeostasis is influenced by neutral lipid metabolites in the lung.
Yang
Li
L
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Yan
Dong
D
Yan
Cong
C
Du
Hong
H
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005799:Genes, Dominant; D017930:Genes, Reporter; D006801:Humans; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000378:metabolism; D007763:Lac Operon; D008024:Ligands; D050356:Lipid Metabolism; D008156:Luciferases / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009924:Organ Culture Techniques; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism; D011485:Protein Binding; D011650:Pulmonary Alveoli / Q000166:cytology; D037701:Pulmonary Surfactant-Associated Protein B / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013229:Stearic Acids / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D001616:beta-Galactosidase / Q000378:metabolism
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D007155:Immunologic Factors; D008024:Ligands; D037701:Pulmonary Surfactant-Associated Protein B; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013229:Stearic Acids; D014157:Transcription Factors; C031183:stearic acid; D008156:Luciferases; D001616:beta-Galactosidase; D015230:Prostaglandin D2