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- W2017169401 abstract "Background High mobility group box 1 (HMGB1) is a critical proinflammatory factor that is closely related to mortality in sepsis patients. Dexmedetomidine has been proven to reduce the mortality rate from endotoxin shock and attenuate endotoxin-induced acute lung injury. These effects result from reduced secretion of many proinflammatory mediators, although it is not clear whether dexmedetomidine affects the secretion of HMGB1. In this study, we explored the effect of dexmedetomidine on the expression and secretion of HMGB1 from lipopolysaccharide (LPS)-activated macrophages. Methods We incubated RAW264.7 cells with LPS in the presence or absence of various concentrations of dexmedetomidine. We used an enzyme-linked immunosorbent assay to detect the secretion levels of HMGB1 in the culture supernatant. We employed real-time polymerase chain reaction to assess the expression of HMGB1 mRNA, and used a nuclear/cytoplasm extraction kit to extract the nuclear and cytoplasmic proteins. We employed Western blotting to observe changes in the translocation of HMGB1 from the nucleus to the cytoplasm. In addition, we used a nuclear factor (NF)-κB p50/p65 transcription factor assay kit to analyze NF-κB activity in the nuclear extract. Results Dexmedetomidine inhibited the translocation of HMGB1 from the nucleus to the cytoplasm and its extracellular secretion in LPS-activated macrophages while suppressing the expression of HMGB1 mRNA. Dexmedetomidine inhibited the translocation of NF-κB from the cytoplasm to the nucleus in LPS-activated macrophages in a dose-dependent manner. Moreover, these effects were significantly reversed by the α2-adrenergic receptor antagonist yohimbine. Conclusions Our study demonstrates that dexmedetomidine inhibits the translocation of HMGB1 from the nucleus to the cytoplasm and the expression of HMGB1 mRNA at clinically relevant dosages. The mechanism responsible for these effects may be through the NF-κB signaling pathway and the α2-adrenergic receptors." @default.
- W2017169401 created "2016-06-24" @default.
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- W2017169401 date "2013-05-01" @default.
- W2017169401 modified "2023-09-27" @default.
- W2017169401 title "Dexmedetomidine inhibits the secretion of high mobility group box 1 from lipopolysaccharide-activated macrophages In vitro" @default.
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- W2017169401 doi "https://doi.org/10.1016/j.jss.2012.07.017" @default.
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