Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Immunopharmacol Immunotoxicol. 2013 Aug;35(4):471-7. doi: 10.3109/08923973.2013.811596.
Since E-selectin-mediated adhesion of leukocytes or tumor cells to the vascular endothelium is a key early event in the initiation of inflammatory response and cancer metastasis, E-selectin inhibition is thought to be a good target for therapeutic intervention. Several flavones have been shown to have anti-inflammatory and anticancer properties. In the present study, we investigated the effects of plant flavones on expression of E-selectin in human umbilical vein endothelial cells. Among 11 flavones, acacetin strongly inhibited TNF-α-induced E-selectin expression in HUVECs. Acacetin suppressed the TNF-α-induced phosphorylation of p38 but did not inhibit TNF-α-induced phosphorylations of JNK and ERK. Acacetin also inhibited the activation of NF-κB by stimulation with TNF-α. Furthermore, adhesion of monocytes to TNF-α-treated endothelial cells was inhibited by cotreatment with acacetin. These results suggest that acacetin inhibits the expression of E-selectin by regulation of the p38 MAPK signaling pathway and activation of NF-κB.
由于 E-选择素介导的白细胞或肿瘤细胞与血管内皮的黏附是炎症反应和癌症转移起始的关键早期事件，因此 E-选择素抑制被认为是治疗干预的一个很好的靶点。几种类黄酮已被证明具有抗炎和抗癌特性。在本研究中，我们研究了植物类黄酮对人脐静脉内皮细胞中 E-选择素表达的影响。在 11 种类黄酮中，阿克替宁强烈抑制 TNF-α诱导的 HUVECs 中 E-选择素的表达。阿克替宁抑制 TNF-α诱导的 p38 磷酸化，但不抑制 TNF-α诱导的 JNK 和 ERK 的磷酸化。阿克替宁还抑制了 TNF-α刺激的 NF-κB 的激活。此外，阿克替宁与 TNF-α处理的内皮细胞共处理可抑制单核细胞与内皮细胞的黏附。这些结果表明，阿克替宁通过调节 p38 MAPK 信号通路和 NF-κB 的激活来抑制 E-选择素的表达。
