title: E. coli endotoxin modulates the expression of Sirtuin proteins in PBMC in humans.
abstract: BACKGROUND
  Sirtuin (SIRT) proteins are class I histone deacetylases displaying gene regulatory functions in inflammatory, cancer, and metabolic diseases. These SIRT actions involve the nuclear factor κ B and its inhibitor I κ B pathway. However, the regulation of SIRT in vivo is still unclear.
  
  
  METHODS
  In a human endotoxemia model, 20 healthy male subjects received an intravenous bolus of 2 ng/kg body weight Escherichia coli endotoxin (LPS). SIRT expression was investigated in peripheral blood mononuclear cells (PBMC) with qPCR and Western blot before and 3 hours, 6 hours, and 24 hours after LPS challenge. Additionally, SIRT regulation was studied in vitro in cultivated PBMC after incubation with 20 ng/mL LPS.
  
  
  RESULTS
  A downregulation by >40% of SIRT1 mRNA was detectable 3 hours after LPS and of SIRT3 mRNA 6 hours after LPS. SIRT3, IκBα, and IκB-β protein expressions were decreased 3 and 6 hours after LPS. SIRT2 mRNA or protein expression did not change following LPS. These findings were consistent in vitro and associated with augmented phosphorylation of IκB-β.
  
  
  CONCLUSIONS
  In this E. coli endotoxemia model, SIRT1 and SIRT3 mRNA expressions in PBMC in humans were reduced after LPS challenge. This suggests that SIRT may represent an inflammatory target protein in vivo.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Angela
authors.initials: A
authors.lastname: Storka
authors.affiliation: Department of Internal Medicine I, Institute of Cancer Research, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Führlinger
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Seper
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Lisa
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Jew
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Asha
authors.initials: A
authors.lastname: Leisser
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Wolzt
mesh_terms: D000328:Adult; D016207:Cytokines / Q000097:blood; D004926:Escherichia coli / Q000472:pathogenicity*; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D016328:NF-kappa B / Q000502:physiology; D054409:Nicotinamide Phosphoribosyltransferase / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D037761:Sirtuins / Q000097:blood / Q000235:genetics / Q000502:physiology*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; D037761:Sirtuins