Sulforaphane reduces vascular inflammation in mice and prevents TNF-α-induced monocyte adhesion to primary endothelial cells through interfering with the NF-κB pathway.
Sulforaphane reduces vascular inflammation in mice and prevents TNF-α-induced monocyte adhesion to primary endothelial cells through interfering with the NF-κB pathway.
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萝卜硫素通过干扰 NF-κB 通路减少小鼠血管炎症，并防止 TNF-α 诱导的单核细胞粘附到原代内皮细胞。
DOI：
10.1016/j.jnutbio.2014.03.011
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发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Jia Z
中科院分区：
文献类型：
--
作者：
Nallasamy P;Si H;Babu PV;Pan D;Fu Y;Brooke EA;Shah H;Zhen W;Zhu H;Liu D;Li Y;Jia Z
萝卜硫素是一种存在于十字花科蔬菜中的天然异硫氰酸酯，因其在体外改善血管功能的潜力而受到广泛关注。然而，其在体内的作用和生理浓度的萝卜硫素的分子机制仍不清楚。在这里，我们报告了低至0.5 μM的莱菔硫烷浓度显著抑制TNF-α诱导的单核细胞与人脐静脉内皮细胞（HUVECs）的粘附，这是静态和流动条件下动脉粥样硬化发病机制中的关键事件。这种生理浓度的莱菔硫烷还显著抑制TNF-α诱导的单核细胞趋化蛋白-1（MCP-1）、粘附分子sVCAM-1和sE-选择素的产生，这些是调节增强的内皮细胞-单核细胞相互作用的关键介质。此外，莱菔硫烷还能抑制TNF-α诱导的内皮细胞NF-κB转录活性、IκBα降解及随后的NF-κB p65核转位，提示莱菔硫烷可能通过抑制NF-κB信号通路而抑制炎症反应。在一项动物研究中，小鼠饲料中的萝卜硫素（300 ppm）显著消除了C57 BL/6小鼠中TNF-α增加的离体单核细胞粘附和循环粘附分子和趋化因子。组织学显示萝卜硫素处理显著防止主动脉内膜层中内皮衬里的爆发，并保留弹性蛋白纤维的精细组织，如Verhoeff-van Gieson染色所示。免疫组织化学研究表明，萝卜硫素治疗还减少了TNF-α治疗小鼠主动脉中VCAM-1和单核细胞衍生的F4/80阳性巨噬细胞。总之，在体外和体内模型中，生理浓度的莱菔硫烷可保护TNF-α诱导的血管内皮炎症。莱菔硫烷的抗炎作用可能至少部分与干扰NF-κB通路有关。
Sulforaphane, a naturally-occurring isothiocyanate present in cruciferous vegetables, has received wide attention for its potential to improve vascular function in vitro. However, its effect in vivo and the molecular mechanism of sulforaphane at physiological concentrations remain unclear. Here, we report that a sulforaphane concentration as low as 0.5 μM significantly inhibited TNF-α-induced adhesion of monocytes to human umbilical vein endothelial cells (HUVECs), a key event in the pathogenesis of atherosclerosis both in static and under flow conditions. Such physiological concentrations of sulforaphane also significantly suppressed TNF-α-induced production of monocyte chemotactic protein-1 (MCP-1), adhesion molecule sVCAM-1 and sE-Selectin, key mediators in the regulation of enhanced endothelial cell-monocyte interaction. Furthermore, sulforaphane inhibited TNF-α-induced NF-κB transcriptional activity, IκBα degradation and subsequent NF-κB p65 nuclear translocation in endothelial cells, suggesting that sulforaphane can inhibit inflammation by suppressing NF-κB signaling. In an animal study, sulforaphane (300 ppm) in a mouse diet significantly abolished TNF-α-increased ex vivo monocyte adhesion and circulating adhesion molecules and chemokines in C57BL/6 mice. Histology showed that sulforaphane treatment significantly prevented the eruption of endothelial lining in the intima layer of the aorta and preserved elastin fibers’ delicate organization as shown by Verhoeff-van Gieson staining. Immunohistochemistry studies showed that sulforaphane treatment also reduced VCAM-1 and monocytes-derived F4/80-positive macrophages in the aorta of TNF-α-treated mice. In conclusion, sulforaphane at physiological concentrations protects against TNF-α-induced vascular endothelial inflammation, in both in vitro and in vivo models. This anti-inflammatory effect of sulforaphane may be, at least in part, associated with interfering with the NF-κB pathway.
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DOI：
10.1158/1078-0432.ccr-09-2937
发表时间：
2010-05-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Li Y;Zhang T;Korkaya H;Liu S;Lee HF;Newman B;Yu Y;Clouthier SG;Schwartz SJ;Wicha MS;Sun D
通讯作者：
Sun D
影响因子：
5.6
作者：
Jayakumar, Thanasekaran;Chen, Wei-Fan;Hsieh, Cheng-Ying
通讯作者：
Hsieh, Cheng-Ying
影响因子：
4.8
作者：
Li, Yan;Reddy, Marpadga A.;Natarajan, Rama
通讯作者：
Natarajan, Rama
Sulforaphane在MCF-7乳腺癌细胞中通过NF-κB信号传导途径（而不是AP-1）控制TPA诱导的MMP-9表达。
影响因子：
3.8
作者：
Lee YR;Noh EM;Han JH;Kim JM;Hwang BM;Kim BS;Lee SH;Jung SH;Youn HJ;Chung EY;Kim JS
通讯作者：
Kim JS
影响因子：
5.8
作者：
Lin, Wen;Wu, Rachel T.;Wu, Tienyuan;Khor, Tin-Oo;Wang, Hu;Kong, Ah-Ng
通讯作者：
Kong, Ah-Ng