Anesthetic propofol reduces endotoxic inflammation by inhibiting reactive oxygen species-regulated Akt/IKKβ/NF-κB signaling

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

Research output: Contribution to journalArticle

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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. 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-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/Significance: These results suggest that propofol reduces LPS-induced inflammatory responses in macrophages by inhibiting the interconnected ROS/Akt/IKKβ/NF-κB signaling pathways.

Original languageEnglish
Article numbere17598
JournalPLoS One
Volume6
Issue number3
DOIs
Publication statusPublished - 2011

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Propofol
anesthetics
lipopolysaccharides
Lipopolysaccharides
Anesthetics
reactive oxygen species
Reactive Oxygen Species
inflammation
Inflammation
Macrophages
macrophages
Chemical activation
Phosphorylation
phosphorylation
Western blotting
Western Blotting
Immunosorbents
Toll-Like Receptor 4
tumor necrosis factors
mice

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Anesthetic propofol reduces endotoxic inflammation by inhibiting reactive oxygen species-regulated Akt/IKKβ/NF-κB signaling. / Hsing, Chung-Hsi; Lin, Ming-Chung; Choi, Pui-Ching; Huang, Wei-Ching; Kai, Jui-In; Tsai, Cheng-Chieh; Cheng, Yi-Lin; Hsieh, Chia-Yuan; Wang, Chi-Yun; Chang, Yu-Ping; Chen, Yu-Hong; Chen, Chia-Ling; Lin, Chiou-Feng.

In: PLoS One, Vol. 6, No. 3, e17598, 2011.

Research output: Contribution to journalArticle

Hsing, C-H, Lin, M-C, Choi, P-C, Huang, W-C, Kai, J-I, Tsai, C-C, Cheng, Y-L, Hsieh, C-Y, Wang, C-Y, Chang, Y-P, Chen, Y-H, Chen, C-L & Lin, C-F 2011, 'Anesthetic propofol reduces endotoxic inflammation by inhibiting reactive oxygen species-regulated Akt/IKKβ/NF-κB signaling', PLoS One, vol. 6, no. 3, e17598. https://doi.org/10.1371/journal.pone.0017598
Hsing, Chung-Hsi ; Lin, Ming-Chung ; Choi, Pui-Ching ; Huang, Wei-Ching ; Kai, Jui-In ; Tsai, Cheng-Chieh ; Cheng, Yi-Lin ; Hsieh, Chia-Yuan ; Wang, Chi-Yun ; Chang, Yu-Ping ; Chen, Yu-Hong ; Chen, Chia-Ling ; Lin, Chiou-Feng. / Anesthetic propofol reduces endotoxic inflammation by inhibiting reactive oxygen species-regulated Akt/IKKβ/NF-κB signaling. In: PLoS One. 2011 ; Vol. 6, No. 3.
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AU - Huang, Wei-Ching

AU - Kai, Jui-In

AU - Tsai, Cheng-Chieh

AU - Cheng, Yi-Lin

AU - Hsieh, Chia-Yuan

AU - Wang, Chi-Yun

AU - Chang, Yu-Ping

AU - Chen, Yu-Hong

AU - Chen, Chia-Ling

AU - Lin, Chiou-Feng

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