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

76 Citations (Scopus)

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

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Anesthetic propofol reduces endotoxic inflammation by inhibiting reactive oxygen species-regulated Akt/IKKβ/NF-κB signaling'. Together they form a unique fingerprint.

  • Cite this

    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, 6(3), [e17598]. https://doi.org/10.1371/journal.pone.0017598