EF24 suppresses maturation and inflammatory response in dendritic cells.
EF24 suppresses maturation and inflammatory response in dendritic cells.
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DOI：
10.1093/intimm/dxr121
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发表时间：
2012-07
影响因子：
4.4
通讯作者：
Prachi Vilekar;S. Awasthi;A. Natarajan;S. Anant;V. Awasthi
中科院分区：
文献类型：
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作者：
Prachi Vilekar;S. Awasthi;A. Natarajan;S. Anant;V. Awasthi
研究了合成类姜黄素 EF24 对小鼠骨髓来源的永生化 JAWS II 树突状细胞 (DC) 成熟和炎症反应的影响。 EF24 降低 LPS 诱导的 MHC II 类、CD80 和 CD86 分子的表达。它还消除了树突的出现，这是成熟树突状细胞的典型特征。这些效应伴随着 LPS 诱导的转录因子核因子 kappa 轻链增强子 (NF-κB) 激活的抑制。还观察到促炎细胞因子 [肿瘤坏死因子 (TNF)-α、IL-6] 在 mRNA 和分泌水平上同时减少。为了研究 LPS 效应对 MyD88 接头蛋白的依赖性，我们用显性失活 MyD88 质粒构建体 (MyD88-DN) 转染 JAWS II DC。 EF24 以 MyD88 依赖性方式降低 NF-κB 活性和 TNF-α 分泌。这些结果表明EF24通过抑制DC的成熟和减少炎性细胞因子的分泌来调节DC。此外，EF24 似乎在 LPS-TLR4/MyD88/NF-κB 途径中的 MyD88 处或其上游起作用。
Synthetic curcuminoid EF24 was studied for its effect on the maturation and inflammatory response in murine bone marrow derived immortalized JAWS II dendritic cells (DCs). EF24 reduced the expression of LPS-induced MHC class II, CD80 and CD86 molecules. It also abrogated the appearance of dendrites, a typical characteristic of mature DCs. These effects were accompanied by the inhibition of LPS-induced activation of transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB). Simultaneous reduction of pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, IL-6] both at the mRNA and secreted levels was also observed. To investigate the dependency of LPS effects on MyD88 adaptor protein, we transfected JAWS II DCs with dominant negative MyD88 plasmid construct (MyD88-DN). EF24 reduced NF-κB activity and TNF-α secretion in a MyD88-dependent manner. These results suggest that EF24 modulates DCs by suppressing their maturation and reducing the secretion of inflammatory cytokines. Further, it appears that EF24 acts at or upstream of MyD88 in the LPS-TLR4/MyD88/NF-κB pathway.