title: The inhibitory effect of lidocaine on the release of high mobility group box 1 in lipopolysaccharide-stimulated macrophages.
abstract: BACKGROUND
  High mobility group box 1 (HMGB1), a key mediator of inflammation, has been shown to inhibit phagocytosis of apoptotic cells in sepsis. Lidocaine has been proven to protect macrophages in mice with septic peritonitis by attenuating the production of cytokines. However, it is currently unknown whether lidocaine also affects HMGB1. In this study, we sought to detect the effect of lidocaine on the release of HMGB1 from RAW264.7 macrophages after lipopolysaccharide (LPS) stimulation.
  
  
  METHODS
  The levels of HMGB1 in the supernatant of RAW264.7 cells incubated with LPS and different concentrations of lidocaine were measured by enzyme-linked immunosorbent assays. HMGB1 mRNA expression was assessed by real-time polymerase chain reaction. The immunocytochemistry was used to detect the release and translocation of HMGB1 from the nucleus to cytoplasm. Nuclear factor (NF)-κB levels in the nuclear fraction of RAW264.7 cells were measured with the Active Motif NF-κB family kit.
  
  
  RESULTS
  We found that lidocaine suppressed the translocation of HMGB1 from the nucleus to cytoplasm and decreased the expression of HMGB1 mRNA in RAW264.7 cells induced by LPS. Furthermore, the LPS-stimulated translocation of NF-κB from the cytoplasm to nucleus was inhibited by lidocaine in a dose-dependent manner.
  
  
  CONCLUSIONS
  Our data suggest that lidocaine functions as an antiinflammatory by inhibiting expression of HMGB1 mRNA, and translocating both HMGB1 and NF-κB from the nucleus to cytoplasm. The mechanism of these effects might be involved, at least partly, in the inhibition of the NF-κB signal pathway.
authors.affiliation: Department of Anesthesiology, Qilu Hospital, Shandong University, 107 Wenhuan Xi Rd., Jinan, Shandong 250012, PR China.
authors.forename: Huan-Liang
authors.initials: HL
authors.lastname: Wang
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Zhang
authors.forename: Wei-Fu
authors.initials: WF
authors.lastname: Lei
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Zhou
authors.forename: Ting
authors.initials: T
authors.lastname: Ye
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008012:Lidocaine / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D016328:NF-kappa B; D008012:Lidocaine