ArticleNan fang yi ke da xue xue bao = Journal of Southern Medical University2018
[Exogenous agmatine inhibits lipopolysaccharide-induced activation and dysfunction of human umbilical vein endothelial cells].
Article in Nan fang yi ke da xue xue bao = Journal of Southern Medical University, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors at 1 institution in 1 country.
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Abstract
objectiveTo investigate whether exogenous agmatine inhibits lipopolysaccharide (LPS)-induced activation and dysfunction of human umbilical vein endothelial cells (HUVECs) by modulating nuclear factor-κB (NF-κB) and MAPK signal pathways and the production of reactive oxygen species (ROS).
methodsCultured HUVECs were treated with agmatine at the optimized concentration of 1.0 mmolγL, LPS (10 µgγmL), and LPS + agmatine, with or without pretreatment with the inhibitors of NF-κB (PDTC), p38 (SB203580), and ERK (PD98059) for 1 h. The levels of soluble vascular cell adhesion molecule 1 (VCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin and monocyte chemoattractant protein 1 (MCP-1) in the supernatant were determined using ELISA, and their mRNA expressions, along with heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO-1), were assessed using real-time PCR. ROS production in the cells was determined using 2, 7-dichlorofluoresce in diacetate (DCFH-DA) as the fluorescence probe. The protein expressions of VCAM-1, ICAM-1, p65, phospho-p65 (p-p65), IκBα, p-IκBα, ERK, p-ERK, p38, p-p38, JNK, and p-JNK were detected using Western blotting.
resultsLPS stimulation for 6 and 24 h significantly increased the levels of sVCAM-1, sICAM-1, sE-selectin and MCP-1 in the supernatant, intracellular ROS production, and the mRNA expressions of these molecules (P<0.05). Intervention with 1 mmolγL agmatine, similar with pretreatment with p38, ERK and NF-κB inhibitors, obviously inhibited such effects of LPS in HUVECs (P<0.05). Agmatine significantly up-regulated the mRNA expression of HO-1 (P<0.05), inhibited LPS-induced phosphorylation of p38, ERK, nuclear p65 and cytoplasmic IκBα, and up-regulated the protein expression of cytoplasmic IκBα.
conclusionAgmatine inhibits LPS-induced activation and dysfunction of HUVECs by modulating NF-κB and MAPK signal pathways to down-regulate the expressions of adhesion molecules and chemokines and by up-regulating the expression of HO-1 to reduce ROS production.
Indexed as
Identifiers
29997086PMC6765718W3025593857What OpenQuestion holds
Registered trials
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