Effects of LOX-1/NF-кB signals on expressions of inflammatory cytokines stimulated by ox-LDL in human umbilical vein endothelial cells and intervention of fluvastatin
Jiang De-qian
Abstract
Jiang De-qian
Abstract
Objective: To investigate effects of lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)/NF(nuclear factor)-κB signals on expressions of inflammatory cytokines stimulated by ox-LDL(oxidized low density lipoprotein) in human umbilical vein endothelial cells(HUVECs) and intervention of fluvastatin.Methods:Ox-LDL stimulated group,LOX-1 neutralizing antibody intervention group,NF-κB inhibitor pyrolidine dithiocarbamate(PDTC) intervention group,fluvastatin intervention group and blank control group were established.The levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in supernatant of all groups were measured.Results: Concentrations of TNF-a in supernatants after 24h stimulation by ox-LDL of 25mg/L,50mg/L and 100mg/L were(32.34±2.46)pg/ml,(96.43±8.36)pg/ml and(62.79±4.64)pg/ml respectively,concentrations of IL-6 were(264.71±15.06)pg/ml,(630.70±17.77)pg/ml and(378.62±16.33)pg/ml respectively,and all these significantly increased compared with those of blank control group [TNF-α:(22.99±3.55)pg/ml,IL-6:(80.37±8.29)pg/ml],P0.05~0.01;after interventions of PDTC and LOX-1 neutralizing antibody,concentrations of TNF-a in supernatants significantly decreased compared with 50mg/L ox-LDL intervention group(P0.01).Concentrations of TNF-a in supernatants after 24h intervention by fluvastatin of 0.01μmol/L、0.1μmol/L、1μmol/L were(73.84±6.50)pg/ml,(42.59±6.45)pg/ml and(23.55±4.27)pg/ml respectively,concentrations of IL-6 were(549.0±20.23)pg/ml,(434.56±22.4)pg/ml and(302.42±21.30)pg/ml respectively,and all these significantly decreased compared with those of 50mg/L ox-LDL intervention group(P0.05~0.01).Conclusion: Ox-LDL can stimulate expressions of TNF-a and IL-6 in supernatant of HUVECs and it shows significant dose-effect relationship in dose range of 25~50mg/L.Fluvastatin may dose-dependently inhibits expressions of TNF-a and IL-6 in supernatant of HUVECs.
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Objective: To investigate effects of lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)/NF(nuclear factor)-κB signals on expressions of inflammatory cytokines stimulated by ox-LDL(oxidized low density lipoprotein) in human umbilical vein endothelial cells(HUVECs) and intervention of fluvastatin.Methods:Ox-LDL stimulated group,LOX-1 neutralizing antibody intervention group,NF-κB inhibitor pyrolidine dithiocarbamate(PDTC) intervention group,fluvastatin intervention group and blank control group were established.The levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in supernatant of all groups were measured.Results: Concentrations of TNF-a in supernatants after 24h stimulation by ox-LDL of 25mg/L,50mg/L and 100mg/L were(32.34±2.46)pg/ml,(96.43±8.36)pg/ml and(62.79±4.64)pg/ml respectively,concentrations of IL-6 were(264.71±15.06)pg/ml,(630.70±17.77)pg/ml and(378.62±16.33)pg/ml respectively,and all these significantly increased compared with those of blank control group [TNF-α:(22.99±3.55)pg/ml,IL-6:(80.37±8.29)pg/ml],P0.05~0.01;after interventions of PDTC and LOX-1 neutralizing antibody,concentrations of TNF-a in supernatants significantly decreased compared with 50mg/L ox-LDL intervention group(P0.01).Concentrations of TNF-a in supernatants after 24h intervention by fluvastatin of 0.01μmol/L、0.1μmol/L、1μmol/L were(73.84±6.50)pg/ml,(42.59±6.45)pg/ml and(23.55±4.27)pg/ml respectively,concentrations of IL-6 were(549.0±20.23)pg/ml,(434.56±22.4)pg/ml and(302.42±21.30)pg/ml respectively,and all these significantly decreased compared with those of 50mg/L ox-LDL intervention group(P0.05~0.01).Conclusion: Ox-LDL can stimulate expressions of TNF-a and IL-6 in supernatant of HUVECs and it shows significant dose-effect relationship in dose range of 25~50mg/L.Fluvastatin may dose-dependently inhibits expressions of TNF-a and IL-6 in supernatant of HUVECs.
Key concepts: Fluvastatin, Medicine, Umbilical vein, Tumor necrosis factor alpha, Proinflammatory cytokine, Pyrrolidine dithiocarbamate, Lipoprotein, Human umbilical vein endothelial cell