title: Anesthetic agent propofol inhibits myeloid differentiation factor 88-dependent and independent signaling and mitigates lipopolysaccharide-mediated reactive oxygen species production in human neutrophils in vitro.
abstract: Engagement of toll-like receptor 4 (TLR4) can activate the myeloid differentiation factor 88 (MyD88)/toll-interleukin-1-resistance domain-containing adapter-inducing interferon-β (TRIF) dependent pathways, inducing production of reactive oxygen species (ROS) in neutrophils. Propofol (PPF) has both anti-oxidant and anti-inflammatory properties. However, the molecular mechanism by which PPF influences human neutrophil function is yet to be elucidated. This study aimed to investigate the influence of PPF on lipopolysaccharide (LPS)-induced reactive oxygen species production in human neutrophils. We isolated neutrophils from the peripheral blood of 10 healthy male donors. Neither 1 µg/ml LPS nor 10-150 μmol/L PPF influenced the rate of neutrophil apoptosis, but PPF significantly inhibited LPS-mediated reactive oxygen species production in a dose-dependent manner. PPF inhibited LPS-induced expression of MyD88, tumor necrosis factor receptor-associated factor 6, and TRIF, but not the expression of interferon regulatory factor 3 or phosphorylation of p47(phox), p38-mitogen-activated protein kinase, and nuclear factor (NF)-κB, particularly in the neutrophils in which MyD88 or TRIF had been silenced by siRNA. The inhibitory effect of PPF on LPS-induced activation of p47(phox), p38-mitogen-activated protein kinase, and NF-κB was partially antagonized by over-expression of MyD88 or TRIF in neutrophils. These observations provide insights into the mechanisms responsible for the anti-inflammatory properties of PPF. PPF reduces LPS-induced production of reactive oxygen species in neutrophils via inhibiting expression of MyD88 and TRIF signaling.
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of China Medical University, 155 Nanjing Street, Heping District, Shenyang 110001, Liaoning Province, China.
authors.forename: Xuli
authors.initials: X
authors.lastname: Ren
authors.affiliation: The College of Clinical Medicine, China Medical University, 92 North Street, Heping District, Shenyang 110001, Liaoning Province, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Lv
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of China Medical University, 155 Nanjing Street, Heping District, Shenyang 110001, Liaoning Province, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Fang
authors.affiliation: Department of Psychology, Jilin Medical College, 5 Jilin Avenue, Fengman District, Jilin 132013, China.
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of China Medical University, 155 Nanjing Street, Heping District, Shenyang 110001, Liaoning Province, China. Electronic address: lvhuangweimed@163.com.
authors.forename: Huangwei
authors.initials: H
authors.lastname: Lv
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of China Medical University, 155 Nanjing Street, Heping District, Shenyang 110001, Liaoning Province, China.
authors.forename: Guannan
authors.initials: G
authors.lastname: He
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of China Medical University, 155 Nanjing Street, Heping District, Shenyang 110001, Liaoning Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Immunology, Foundational Institute of China Medical University, 92 North Street, Heping District, Shenyang 110001, Liaoning Province, China.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Laboratory of Hematology, the First Affiliated Hospital of China Medical University, 155 Nanjing Street, Heping District, Shenyang 110001, Liaoning Province, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000328:Adult; D000777:Anesthetics / Q000494:pharmacology*; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000777:Anesthetics; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D007375:Interleukin-1; D008070:Lipopolysaccharides; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C470409:TICAM1 protein, human; D048029:TNF Receptor-Associated Factor 6; D051197:Toll-Like Receptor 4; D048051:p38 Mitogen-Activated Protein Kinases; D015742:Propofol
keywords: MyD88; Neutrophils; Propofol; Reactive oxygen species; Toll-interleukin-1-resistance domain-containing adapter-inducing interferon-β