In vitro study on injury effect of IL-18 activating NF-κB cell signal pathway on human umbilical vein endothelial cells / 重庆医学

ABSTRACT

Objective To investigate the influence of proinflammatory factor interleukin-18(IL-18) on vein endothelial cell function by activating NF-κB mediated cell signal pathway and its association with deep vein thrombosis(DVT).Methods Recombinant human IL-18 was used to act on in vitro cultured human umbilical vein endothelial cell(HUVECs).The NF-κB activation inhibitor was used to conduct interference.The detection measures of real time fluorescence quantitative PCR,Western blot,immunofluorescence and flow cytometry were used to verify whether IL-18 affect the expression of endothelial cellular function markers such as HUVECs normal statusand vWF,P-selectin and tissue plasminogen activator(t-PA) by activating NF-κB mediated cell signal pathway.Moreover the mechanism of IL-18 participating in the DVT was performed the comprehensive analysis by combining with previous study.Results IL-18 could activate NF-κB in endothelial cell,increased the p65 expression in nucleus,decreased the intracellular IκBα expression and significantly increased early apoptosis cells in HUVECs;adding QNZ(EVP4593) could significantly inhibit the activation effect of IL-18 on NF-κB,the occurrence of cellular injury and apoptosis was significantly reduced;IL-18 could promote the abnormal expression of DVT related endothelial cell markers vWF,P-selectin and t-PA (P<0.05).But various markers could recover conventional expression after inhibiting NF-κB activation.Conclusion The interaction between Il-18 and NF-κB causes the abnormality of HUVECs growth status and function,which may be the DVT onset related pathogenic mechanism.