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Inhibition of STAT3 phosphorylation by sulforaphane reduces adhesion molecule expression in vascular endothelial cell

机译:萝卜硫烷对STAT3磷酸化的抑制作用降低血管内皮细胞黏附分子的表达

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Intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) play key roles in the initiation of vascular inflammation. In this study, we explored whether sulforaphane, a dietary phytochemical, can inhibit the expression of ICAM-1 and VCAM-1 in human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS), and the mechanisms involved. Sulforaphane prevented the LPS-mediated increase in ICAM-1 and VCAM-1 expression, (P < 0.01) in HUVEC. Sulforaphane also prevented the LPS-mediated increase in the phosphorylation of signal transducer and activator of transcription 3 (STAT3) (P < 0.01). Stattic, a STAT3 inhibitor, reduced the LPS-induced expression of ICAM-1 and VCAM-1, and STAT3 phosphorylation (P < 0.01). STAT3 small interfering RNA treatment reduced the LPS-induced expression of ICAM-1, VCAM-1, and STAT3 (P < 0.01). Sulforaphane reduced LPS-mediated THP-1 monocyte adhesion to HUVEC (P < 0.01). In C57BL/6 mice, injection of LPS increased aortic ICAM-1 and VCAM-1 expression, and this effect was prevented by sulforaphane. These data provide insight into the mechanism through which sulforaphane partly reduces the expression of ICAM-1 and VCAM-1 on the vascular wall by inhibiting STAT3 phosphorylation.
机译:细胞间粘附分子1(ICAM-1)和血管细胞粘附分子1(VCAM-1)在引发血管炎症中起关键作用。在这项研究中,我们探讨了饮食植物化学物质萝卜硫素是否可以抑制脂多糖(LPS)刺激的人脐静脉内皮细胞(HUVEC)中ICAM-1和VCAM-1的表达,以及涉及的机制。萝卜硫素阻止HUVEC中LPS介导的ICAM-1和VCAM-1表达增加(P <0.01)。萝卜硫烷还阻止了LPS介导的信号转导子和转录激活子3(STAT3)的磷酸化增加(P <0.01)。 Stattic(一种STAT3抑制剂)可降低LPS诱导的ICAM-1和VCAM-1的表达以及STAT3磷酸化(P <0.01)。 STAT3小干扰RNA处理降低了LPS诱导的ICAM-1,VCAM-1和STAT3的表达(P <0.01)。萝卜硫烷降低了LPS介导的THP-1单核细胞对HUVEC的粘附(P <0.01)。在C57BL / 6小鼠中,注射LPS可增加主动脉ICAM-1和VCAM-1的表达,而萝卜硫烷可阻止这种作用。这些数据提供了对萝卜硫烷通过抑制STAT3磷酸化而部分减少ICAM-1和VCAM-1在血管壁上表达的机制的深入了解。

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