PMID- 25446563 OWN - NLM STAT- MEDLINE DCOM- 20150807 LR - 20141208 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 744 DP - 2014 Dec 5 TI - 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. PG - 164-72 LID - S0014-2999(14)00737-7 [pii] LID - 10.1016/j.ejphar.2014.10.030 [doi] AB - Engagement of toll-like receptor 4 (TLR4) can activate the myeloid differentiation factor 88 (MyD88)/toll-interleukin-1-resistance domain-containing adapter-inducing interferon-beta (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 microg/ml LPS nor 10-150 mumol/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)-kappaB, 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-kappaB 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. CI - Copyright (c) 2014 Elsevier B.V. All rights reserved. FAU - Ren, Xuli AU - Ren X AD - Department of Anesthesiology, the First Affiliated Hospital of China Medical University, 155 Nanjing Street, Heping District, Shenyang 110001, Liaoning Province, China. FAU - Lv, Fei AU - Lv F AD - The College of Clinical Medicine, China Medical University, 92 North Street, Heping District, Shenyang 110001, Liaoning Province, China. FAU - Fang, Bo AU - Fang B AD - Department of Anesthesiology, the First Affiliated Hospital of China Medical University, 155 Nanjing Street, Heping District, Shenyang 110001, Liaoning Province, China. FAU - Liu, Song AU - Liu S AD - Department of Psychology, Jilin Medical College, 5 Jilin Avenue, Fengman District, Jilin 132013, China. FAU - Lv, Huangwei AU - Lv H AD - 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. FAU - He, Guannan AU - He G AD - Department of Anesthesiology, the First Affiliated Hospital of China Medical University, 155 Nanjing Street, Heping District, Shenyang 110001, Liaoning Province, China. FAU - Ma, Hong AU - Ma H AD - Department of Anesthesiology, the First Affiliated Hospital of China Medical University, 155 Nanjing Street, Heping District, Shenyang 110001, Liaoning Province, China. FAU - Cao, Yaming AU - Cao Y AD - Department of Immunology, Foundational Institute of China Medical University, 92 North Street, Heping District, Shenyang 110001, Liaoning Province, China. FAU - Wang, Yue AU - Wang Y AD - Laboratory of Hematology, the First Affiliated Hospital of China Medical University, 155 Nanjing Street, Heping District, Shenyang 110001, Liaoning Province, China. LA - eng PT - Journal Article DEP - 20141028 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Adaptor Proteins, Vesicular Transport) RN - 0 (Anesthetics) RN - 0 (IRF3 protein, human) RN - 0 (Interferon Regulatory Factor-3) RN - 0 (Interleukin-1) RN - 0 (Lipopolysaccharides) RN - 0 (MYD88 protein, human) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (NF-kappa B) RN - 0 (Reactive Oxygen Species) RN - 0 (TICAM1 protein, human) RN - 0 (TNF Receptor-Associated Factor 6) RN - 0 (Toll-Like Receptor 4) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - YI7VU623SF (Propofol) SB - IM MH - Adaptor Proteins, Vesicular Transport/metabolism MH - Adult MH - Anesthetics/*pharmacology MH - Humans MH - Interferon Regulatory Factor-3/metabolism MH - Interleukin-1/metabolism MH - Lipopolysaccharides MH - Male MH - Myeloid Differentiation Factor 88/*metabolism MH - NF-kappa B/metabolism MH - Neutrophils/*drug effects/metabolism MH - Phosphorylation/drug effects MH - Propofol/*pharmacology MH - Reactive Oxygen Species/*metabolism MH - Signal Transduction/*drug effects MH - TNF Receptor-Associated Factor 6/metabolism MH - Toll-Like Receptor 4/metabolism MH - p38 Mitogen-Activated Protein Kinases/metabolism OTO - NOTNLM OT - MyD88 OT - Neutrophils OT - Propofol OT - Reactive oxygen species OT - Toll-interleukin-1-resistance domain-containing adapter-inducing interferon-beta EDAT- 2014/12/03 06:00 MHDA- 2015/08/08 06:00 CRDT- 2014/12/03 06:00 PHST- 2014/04/04 00:00 [received] PHST- 2014/10/11 00:00 [revised] PHST- 2014/10/14 00:00 [accepted] PHST- 2014/12/03 06:00 [entrez] PHST- 2014/12/03 06:00 [pubmed] PHST- 2015/08/08 06:00 [medline] AID - S0014-2999(14)00737-7 [pii] AID - 10.1016/j.ejphar.2014.10.030 [doi] PST - ppublish SO - Eur J Pharmacol. 2014 Dec 5;744:164-72. doi: 10.1016/j.ejphar.2014.10.030. Epub 2014 Oct 28.