Molecular insights into the differences in anti-inflammatory activities of green tea catechins on IL-1β signaling in rheumatoid arthritis synovial fibroblasts.
Molecular insights into the differences in anti-inflammatory activities of green tea catechins on IL-1β signaling in rheumatoid arthritis synovial fibroblasts.
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DOI：
10.1016/j.taap.2017.05.016
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发表时间：
2017-08-15
影响因子：
3.8
通讯作者：
Ahmed S
中科院分区：
文献类型：
--
作者：
Fechtner S;Singh A;Chourasia M;Ahmed S
在这项研究中，我们发现，在绿色茶中发现的儿茶素（EGCG，EGC和EC）差异干扰IL-1β信号通路，该通路调节促炎介质（IL-6和IL-8）和考克斯-2在原代人类风湿性关节炎滑膜成纤维细胞（RASFs）中的表达。EGCG和EGC抑制IL-6、IL-8和MMP-2的产生，并选择性地抑制考克斯-2的表达。EC没有表现出任何抑制作用。当我们观察IL-1β信号通路中关键信号蛋白的表达时，我们发现所有测试的儿茶素都可以抑制TAK-1活性。因此，绿色茶的消费提供了整体抗炎作用。分子对接分析证实，EGCG，EGC和EC都占据了TAK 1激酶结构域的活性位点。然而，EGCG占据了TAK 1活性位点的大部分。EGCG除抑制TAK 1外，还能抑制P38和核NF-κB的表达，而EC和EGC对TAK 1的抑制作用不明显。我们的研究结果表明，与消费绿色茶相关的主要健康益处之一是由于EGCG和EGC的活性，它们都以较高的量存在。虽然EGCG是抑制下游炎症信号传导的最有效的儿茶素，但其有效性可能会受到EC存在的阻碍。因此，不同的EC含量在绿色茶可能会降低其他潜在的儿茶素在绿色茶的抗炎作用。
In this study, we found that catechins found in green tea (EGCG, EGC, and EC) differentially interfere with the IL-1β signaling pathway which regulates the expression of pro-inflammatory mediators (IL-6 and IL-8) and Cox-2 in primary human rheumatoid arthritis synovial fibroblasts (RASFs). EGCG and EGC inhibited IL-6, IL-8, and MMP-2 production and selectively inhibited Cox-2 expression. EC did not exhibit any inhibitory effects. When we looked at the expression of key signaling proteins in the IL-1β signaling pathway, we found all the tested catechins could inhibit TAK-1 activity. Therefore, the consumption of green tea offers an overall anti-inflammatory effect. Molecular docking analysis confirms that EGCG, EGC, and EC all occupy the active site of the TAK1 kinase domain. However, EGCG occupies the majority of the TAK1 active site. In addition to TAK1 inhibition, EGCG can also inhibit P38 and nuclear NF-κB expression whereas EC and EGC were not effective inhibitors. Our findings suggest one of the main health benefits associated with the consumption of green tea are due to the activity of EGCG and EGC which are both present at higher amounts. Although EGCG is the most effective catechin at inhibiting downstream inflammatory signaling, its effectiveness could be hindered by the presence of EC. Therefore, varying EC content in green tea may reduce the anti-inflammatory effects of other potential catechins in green tea.
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DOI：
10.1155/2012/505842
发表时间：
2012
期刊：
Arthritis
影响因子：
--
作者：
Ribel-Madsen S;Bartels EM;Stockmarr A;Borgwardt A;Cornett C;Danneskiold-Samsøe B;Bliddal H
通讯作者：
Bliddal H
影响因子：
3
作者：
Marsico, Fabio;Paolillo, Stefania;Filardi, Pasquale P.
通讯作者：
Filardi, Pasquale P.
影响因子：
8
作者：
Bigelow, RLH;Cardelli, JA
通讯作者：
Cardelli, JA
影响因子：
4.9
作者：
Ahmed S
通讯作者：
Ahmed S
影响因子：
4.8
作者：
Ninomiya-Tsuji, J;Kajino, T;Matsumoto, K
通讯作者：
Matsumoto, K