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Anesthesiology and Pain Management


Anesthetic Propofol Reduces Endotoxic Inflammation by Inhibiting Reactive Oxygen Species-regulated Akt/IKKß/NF-?B Signaling
Published: Tuesday, March 08, 2011
Author: Chung-Hsi Hsing et al.

by Chung-Hsi Hsing, Ming-Chung Lin, Pui-Ching Choi, Wei-Ching Huang, Jui-In Kai, Cheng-Chieh Tsai, Yi-Lin Cheng, Chia-Yuan Hsieh, Chi-Yun Wang, Yu-Ping Chang, Yu-Hong Chen, Chia-Ling Chen, Chiou-Feng Lin

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.

Methodology/Principal Findings

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-a (TNF-a), 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 IKKß (Ser180) and nuclear factor (NF)-?B (Ser536); the subsequent nuclear translocation of NF-?B 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-?B 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/Significance

These results suggest that propofol reduces LPS-induced inflammatory responses in macrophages by inhibiting the interconnected ROS/Akt/IKKß/NF-?B signaling pathways.

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