title: Etomidate Mitigates Lipopolysaccharide-Induced CD14 and TREM-1 Expression, NF-κB Activation, and Pro-inflammatory Cytokine Production in Rat Macrophages.
abstract: This study was aimed at investigating the effect of etomidate on the viability of rat macrophages and the function of lipopolysaccharide (LPS)-stimulated macrophages as well as the potential mechanisms. Rat macrophages were isolated and treated with different doses of etomidate for 24 h, and their viability was determined by the CCK-8 assay. Furthermore, macrophages were treated with, or without, 1 μg/ml of LPS, and/or 2.5 or 5 μM etomidate in the presence or absence of a TREM-1 inhibitor (LP17, 100 ng/ml), and the levels of TNF-α, IL-6, CD14, and TREM-1 in the different groups of cells were determined by quantitative RT-PCR, ELISA, and Western blot assays. The levels of NF-κB activation in the different groups of cells were analyzed by an electrophoretic mobility shift assay (EMSA). Etomidate at 31.25 μM or a low dose did not affect the viability of rat macrophages, while etomidate at higher doses reduced the viability of macrophages in vitro. Treatment with 2.5 or 5 μM etomidate or with LP17 alone did not affect the levels of TNF-α, IL-6, CD-14, and TREM-1 in macrophages. Treatment with etomidate significantly mitigated LPS-stimulated TNF-α, IL-6, CD-14, and TREM-1 expression (p < 0.05 for all) and inhibited LPS-induced NF-κB activation in macrophages in vitro. However, treatment with both etomidate and LP17 did not enhance the inhibitory effects in macrophages. Hence, etomidate mitigates LPS-up-regulated pro-inflammatory cytokine production and inhibits LPS-enhanced CD14 and TREM-1 expression and NF-κB activation in macrophages.
authors.affiliation: Department of Anesthesiology, The Second Hospital of Dalian Medical University, 467 Zhongshan Road, Dalian, Liaoning Province, 116027, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, The Second Hospital of Dalian Medical University, 467 Zhongshan Road, Dalian, Liaoning Province, 116027, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The Second Hospital of Dalian Medical University, 467 Zhongshan Road, Dalian, Liaoning Province, 116027, China. jyxiong0639@163.com.
authors.forename: Jun-Yu
authors.initials: JY
authors.lastname: Xiong
authors.affiliation: Laboratory of Molecular Biology, the Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Biology, the Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Lv
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation / Q000187:drug effects; D005045:Etomidate / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000378:metabolism*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000276:immunology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011971:Receptors, Immunologic; C547511:TREM1 protein, rat; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha; D005045:Etomidate
keywords: NF-κB; etomidate; inflammation; lipopolysaccharide; macrophages; sepsis