Anthocyanins from Black Soybean Seed Coats Preferentially Inhibit TNF-α-Mediated Induction of VCAM-1 over ICAM-1 through the Regulation of GATAs and IRF-1
Anthocyanins from Black Soybean Seed Coats Preferentially Inhibit TNF-α-Mediated Induction of VCAM-1 over ICAM-1 through the Regulation of GATAs and IRF-1
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DOI：
10.1021/jf900856z
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发表时间：
2009-08-26
影响因子：
6.1
通讯作者：
Kim, Hye Jung
中科院分区：
文献类型：
--
作者：
Nizamutdinova, Irina Tsoy;Kim, Young Min;Kim, Hye Jung
粘附分子在病理性炎症中具有关键作用。因此，我们研究了花青素对TNF-α诱导细胞间粘附分子-1（ICAM-1）和血管细胞粘附分子-1（VCAM-1）的影响，以及花青素差异调节ICAM-1和VCAM-1表达的可能分子机制。用TNF-α刺激细胞增加ICAM-1和VCAM-1表达，用花青素预处理抑制VCAM-1表达，但不抑制ICAM-1表达。我们发现，IRF-1和GATA，特别是加塔-4和-6，参与TNF-α介导的VCAM-1的表达，但不参与ICAM-1的表达，花青素降低了加塔-4和加塔-6以及IRF-1的核水平。此外，用Jak/STAT抑制剂预处理降低TNF-α诱导的VCAM-1表达和核加塔-4、加塔-6和IRF-1水平。此外，花青素有效地抑制STAT-3的磷酸化。这表明花青素通过Jak/STAT-3活化调节加塔和IRF-1结合活性，差异调节TNF-α介导的VCAM-1和ICAM-1表达。
Adhesion molecules have a key role in pathological inflammation. Thus, we investigated the effect of anthocyanins on the induction of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by TNF-alpha and the possible molecular mechanisms by which anthocyanins differentially regulate ICAM-1 and VCAM-1 expression. Stimulation of cells with TNF-alpha increased ICAM-1 and VCAM-1 expression, and pretreatment with anthocyanins inhibited VCAM-1 expression, but not ICAM-1 expression. We found that IRF-1 and GATAs, especially GATA-4 and -6, were involved in the TNF-alpha-mediated expression of VCAM-1 but not ICAM-1, and anthocyanins decreased nuclear levels of GATA-4 and GATA-6 as well as IRF-1. Moreover, pretreatment with a Jak/STAT inhibitor decreased TNF-alpha-induced VCAM-1 expression and nuclear GATA-4, GATA-6, and IRF-1 levels. Furthermore, anthocyanins efficiently inhibited the phosphorylation of STAT-3. This suggests that anthocyanins differentially regulate TNF-alpha-mediated expression of VCAM-1 and ICAM-1 through modulation of the GATA and IRF-1 binding activity via Jak/STAT-3 activation.