E. coliEndotoxin Modulates the Expression of Sirtuin Proteins in PBMC in Humans
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 factorκB and its inhibitor IκB pathway. However, the regulation of SIRTin vivois still unclear.Material and Methods. In a human endotoxemia model, 20 healthy male subjects received an intravenous bolus of 2 ng/kg body weightEscherichia coliendotoxin (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 studiedin vitroin 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-βprotein expressions were decreased 3 and 6 hours after LPS. SIRT2 mRNA or protein expression did not change following LPS. These findings were consistentin vitroand associated with augmented phosphorylation of IκB-β.Discussion. In thisE. coliendotoxemia model, SIRT1 and SIRT3 mRNA expressions in PBMC in humans were reduced after LPS challenge. This suggests that SIRT may represent an inflammatory target proteinin vivo.