Xuebijing injection inhibits TLR4 signaling pathway through up-regulating ADAM17 activity in EA.hy926 cells
This study was performed to investigate the inhibitory effects of Xuebijing injection(XBJ)on lipopolysaccharide(LPS)-induced inflammatory signals on EA.hy926 vascular endothelial cells and the underlying mechanism,and to provide a theoretical basis for the treatment of sepsis with XBJ.WST-1 assay was used to detect the effects of XBJ on the cell viability;Western blot analysis was performed to detect the protein expression levels of IκBα,p-p65,p-ERK,p-JNK,p-p38,p-AMAD17 in cell lysates and the content of sTLR4 fragment in the concentrated culture supernatants.ADAM17 sheddase activity in cells was detected by using a commercial available kit.Data showed that all of the TLR4-mediated inflammatory signals were significantly inhibited by the treatment of XBJ(P＜0.01).ADAM17 phosphorylation and shedding activity were induced by XBJ treatment,simultaneously the sTLR4 contents in the culture media were increased.XBJ-induced shedding of TLR4 was suppressed by the preteatment of 10 μmol/L TAPI-1(an ADAM17 inhibitor).Taken together,XBJ can induce the shedding of TLR4 from cell membrane by up-regulating ADAM17 shedding activity,thereby inhibiting the activation of TLR4-mediated intracellular inflammatory signals in EA.hy926 cells.
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维普
