title: Human mannose-binding lectin 2 is directly regulated by peroxisome proliferator-activated receptors via a peroxisome proliferator responsive element.
abstract: Human mannose-binding lectin (MBL) is encoded by the MBL2 gene and is a key player in innate immunity. However, the mechanism of the transcriptional regulation of MBL2 is largely unknown. The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that play an important role in a number of biological responses, including lipid homeostasis, immune function and adipogenesis. In this study, we showed that PPARα and PPARγ up-regulate the expression of human MBL2. Using a luciferase assay, electrophoretic mobility-shift assay and chromatin immunoprecipitation assay, we demonstrated that PPARs regulate the expression of human MBL2 via the peroxisome proliferator responsive element (PPRE). On the other hand, MBL2 mRNA expression was not affected by the PPARα ligand both in vivo in rat liver and in vitro in rat H4IIE hepatoma cells. Thus, there is a species difference in regulation of MBL2 gene expression by PPARs between humans and rodents. We also show that the species differences in response to PPAR could be due in part to sequence-specific differences in the PPRE in the promoter region of MBL2. These results indicate that human, but not rat, MBL2 expression is regulated by PPARs via a PPRE.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tachibana
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Inada
authors.forename: Ken
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishimoto
authors.forename: Masanori
authors.initials: M
authors.lastname: Yamashita
authors.forename: Takashi
authors.initials: T
authors.lastname: Maegawa
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamasaki
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Osada
authors.forename: Toshiya
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.forename: Takao
authors.initials: T
authors.lastname: Hamakubo
authors.forename: Juro
authors.initials: J
authors.lastname: Sakai
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Takefumi
authors.initials: T
authors.lastname: Doi
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D047493:PPAR alpha / Q000235:genetics* / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020218:Response Elements; D015398:Signal Transduction; D013045:Species Specificity
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D047493:PPAR alpha; D047495:PPAR gamma; D008156:Luciferases
keywords: MBL2; PPAR alpha; PPAR gamma; PPRE; species difference