title: Anesthetic propofol reduces endotoxic inflammation by inhibiting reactive oxygen species-regulated Akt/IKKβ/NF-κB signaling.
abstract: BACKGROUND
  Anesthetic propofol has immunomodulatory effects, particularly in the area of anti-inflammation. Bacterial endotoxin lipopolysaccharide (LPS) induces inflammation through toll-like receptor (TLR) 4 signaling. We investigated the molecular actions of propofol against LPS/TLR4-induced inflammatory activation in murine RAW264.7 macrophages.
  
  
  RESULTS
  Non-cytotoxic levels of propofol reduced LPS-induced inducible nitric oxide synthase (iNOS) and NO as determined by western blotting and the Griess reaction, respectively. Propofol also reduced the production of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 as detected by enzyme-linked immunosorbent assays. Western blot analysis showed propofol inhibited LPS-induced activation and phosphorylation of IKKβ (Ser180) and nuclear factor (NF)-κB (Ser536); the subsequent nuclear translocation of NF-κB p65 was also reduced. Additionally, propofol inhibited LPS-induced Akt activation and phosphorylation (Ser473) partly by reducing reactive oxygen species (ROS) generation; inter-regulation that ROS regulated Akt followed by NF-κB activation was found to be crucial for LPS-induced inflammatory responses in macrophages. An in vivo study using C57BL/6 mice also demonstrated the anti-inflammatory properties against LPS in peritoneal macrophages.
  
  
  CONCLUSIONS
  These results suggest that propofol reduces LPS-induced inflammatory responses in macrophages by inhibiting the interconnected ROS/Akt/IKKβ/NF-κB signaling pathways.
authors.affiliation: Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan. hsing@mail.chimei.org.tw
authors.forename: Chung-Hsi
authors.initials: CH
authors.lastname: Hsing
authors.forename: Ming-Chung
authors.initials: MC
authors.lastname: Lin
authors.forename: Pui-Ching
authors.initials: PC
authors.lastname: Choi
authors.forename: Wei-Ching
authors.initials: WC
authors.lastname: Huang
authors.forename: Jui-In
authors.initials: JI
authors.lastname: Kai
authors.forename: Cheng-Chieh
authors.initials: CC
authors.lastname: Tsai
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Cheng
authors.forename: Chia-Yuan
authors.initials: CY
authors.lastname: Hsieh
authors.forename: Chi-Yun
authors.initials: CY
authors.lastname: Wang
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Chang
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Chen
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Chen
authors.forename: Chiou-Feng
authors.initials: CF
authors.lastname: Lin
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004731:Endotoxins / Q000633:toxicity*; D004789:Enzyme Activation / Q000187:drug effects; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018686:Anesthetics, Intravenous; D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase; D015742:Propofol