title: Effects of propofol on lipopolysaccharide-induced expression and release of HMGB1 in macrophages.
abstract: This study aimed to determine the effects of different concentrations of propofol (2,6-diisopropylphenol) on lipopolysaccharide (LPS)-induced expression and release of high-mobility group box 1 protein (HMGB1) in mouse macrophages. Mouse macrophage cell line RAW264.7 cells were randomly divided into 5 treatment groups. Expression levels of HMGB1 mRNA were detected using RT-PCR, and cell culture supernatant HMGB1 protein levels were detected using enzyme-linked immunosorbent assay (ELISA). Translocation of HMGB1 from the nucleus to the cytoplasm in macrophages was observed by Western blotting and activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus was detected using ELISA. HMGB1 mRNA expression levels increased significantly in the cell culture supernatant and in cells after 24 h of stimulating RAW264.7 cells with LPS (500 ng/mL). However, HMGB1 mRNA expression levels in the P2 and P3 groups, which received 500 ng/mL LPS with 25 or 50 μmol/mL propofol, respectively, were significantly lower than those in the group receiving LPS stimulation (P<0.05). After stimulation by LPS, HMGB1 protein levels were reduced significantly in the nucleus but were increased in the cytoplasm (P<0.05). Simultaneously, the activity of NF-κB was enhanced significantly (P<0.05). After propofol intervention, HMGB1 translocation from the nucleus to the cytoplasm and NF-κB activity were inhibited significantly (each P<0.05). Thus, propofol can inhibit the LPS-induced expression and release of HMGB1 by inhibiting HMGB1 translocation and NF-κB activity in RAW264.7 cells, suggesting propofol may be protective in patients with sepsis.
authors.affiliation: Department of Anesthesiology, the Third Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, the Third Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: X Y
authors.initials: XY
authors.lastname: Wei
authors.affiliation: Department of Anesthesiology, the Third Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, the Third Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: L J
authors.initials: LJ
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, the Third Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: L H
authors.initials: LH
authors.lastname: Jiang
mesh_terms: D021581:Active Transport, Cell Nucleus; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D024243:HMGB1 Protein / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D015742:Propofol / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D018686:Anesthetics, Intravenous; D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D015742:Propofol