title: Transcriptional Regulation of the Group IIA Secretory Phospholipase A2 Gene by C/EBPδin Rat liver and its Relationship to Hepatic Gluconeogenesis during Sepsis.
abstract: BACKGROUND
  The present study was undertaken to test hypothesis that altered transcription of secretory Phospholipase A2 (sPLA2) gene in rat liver is regulated by CCAAT/enhancer binding protein δ (C/EBPδ), and to assess its relationship to hepatic gluconeogenesis during the progression of sepsis.
  
  
  METHODS
  Sepsis was induced by Cecal Ligation and Puncture (CLP). Experiments were divided into three groups, control, early sepsis (9 h after CLP), and late sepsis (18 h after CLP).
  
  
  RESULTS
  DNA mobility and super shift assays reveal that C/EBP complexes in the liver consisted of at least three isoforms: C/EBPα, C/EBPβ, and C/EBPδ; and various C/EBP isoforms were capable of interacting with each other. Hepatocyte transfection experiments demonstrate that under normal conditions, binding of C/EBPδ to sPLA2 gene enhanced sPLA2 promoter activity and the binding resulted in an increase in hepatic gluconeogenesis. Under pathological conditions such as sepsis, binding of C/EBPδ to sPLA2 promoter increased during early and late phases of sepsis, and the increases in C/EBPδ binding correlated with increases in sPLA2 mRNA abundance and sPLA2 protein levels. Under otherwise the identical experimental conditions, hepatic gluconeogenesis was reduced during early and late phases of sepsis and the sepsis-induced reductions in liver gluconeogenesis were aggravated by binding of C/EBPδ to sPLA2 gene.
  
  
  CONCLUSIONS
  These results link C/EBPδ binding to altered sPLA2 promoter, and to hepatic gluconeogenesis under normal and pathological conditions. It is suggested that C/EBPδ-sPLA2- hepatic gluconeogenesis may function as a signalling axis affecting glucose homeostasis during the progression of sepsis.
authors.affiliation: Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan ; Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Rei-Cheng
authors.initials: RC
authors.lastname: Yang
authors.affiliation: Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chin
authors.initials: C
authors.lastname: Hsu
authors.affiliation: Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Tzu-Ying
authors.initials: TY
authors.lastname: Lee
authors.affiliation: Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Kung-Kai
authors.initials: KK
authors.lastname: Kuo
authors.affiliation: School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shou-Mei
authors.initials: SM
authors.lastname: Wu
authors.affiliation: Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan ; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 802, Taiwan.
authors.forename: Yen-Hsu
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Ho
authors.affiliation: Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri 63104-1004, USA.
authors.forename: Xing-Hai
authors.initials: XH
authors.lastname: Yao
authors.affiliation: Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri 63104-1004, USA.
authors.forename: Chia-Hsiung
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 802, Taiwan ; Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri 63104-1004, USA.
authors.forename: Maw-Shung
authors.initials: MS
authors.lastname: Liu
keywords: CCAAT/enhancer binding protein δ (C/EBPδ); Liver gluconeogenesis; Secretory Phospholipase A2 (sPLA2); Sepsis; Transcriptional factors; Transcriptional regulation