Binding mode of CpG oligodeoxynucleotides to nanoparticles regulates bifurcated cytokine induction via Toll-like receptor 9.

Binding mode of CpG oligodeoxynucleotides to nanoparticles regulates bifurcated cytokine induction via Toll-like receptor 9.
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DOI:
10.1038/srep00534
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发表时间:
2012
期刊:
影响因子:
4.6
通讯作者:
Hanagata, Nobutaka
Hanagata, Nobutaka
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chinnathambi, Shanmugavel;Chen, Song;Ganesan, Singaravelu;Hanagata, Nobutaka

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胞嘧啶-磷酸-鸟嘌呤寡脱氧核苷酸(cytosine-phosphate-guanine oligodeoxynucleotides,CpG ODNs)与Toll样受体9(Toll like receptor 9,TLR9)的相互作用激活免疫系统。多聚体A类CpG ODN诱导干扰素-α(IFN-α),并且在较小程度上诱导白细胞介素-6。相反,单体B类CpG ODN诱导白细胞介素-6,但不诱导IFN-α。这种差异表明CpG ODN分子的多聚化是IFN-α诱导的关键因素。我们将完全由磷酸二酯骨架组成的B类CpG ODN 2006 x3-PD分子多聚化到具有各种结合模式的量子点硅纳米颗粒上。在此,我们提出了细胞因子诱导的结合模式依赖性分叉,并讨论了CpG ODN和TLR9相互作用的可能机制。我们的发现还表明,纳米颗粒不仅在传递CpG ODN中发挥作用,而且还控制CpG ODN的活性。
The interaction of cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) with Toll-like receptor 9 (TLR9) activates the immune system. Multimeric class A CpG ODNs induce interferon-α (IFN-α) and, to a lesser extent, interleukin-6. By contrast, monomeric class B CpG ODNs induce interleukin-6 but not IFN-α. This difference suggests that the multimerization of CpG ODN molecules is a key factor in IFN-α induction. We multimerized class B CpG ODN2006x3-PD molecules that consist entirely of a phosphodiester backbone onto quantum dot silicon nanoparticles with various binding modes. Herein, we present the binding mode–dependent bifurcation of cytokine induction and discuss its possible mechanism of CpG ODN and TLR9 interaction. Our discoveries also suggest that nanoparticles play roles in not only delivery of CpG ODNs but also control of CpG ODN activity.
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