The effect of alloferon on the enhancement of NK cell cytotoxicity against cancer via the up-regulation of perforin/granzyme B secretion

The effect of alloferon on the enhancement of NK cell cytotoxicity against cancer via the up-regulation of perforin/granzyme B secretion
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DOI:
10.1016/j.imbio.2012.12.002
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发表时间:
2013-08-01
期刊:
影响因子:
2.8
通讯作者:
Lee, Wang Jae
Lee, Wang Jae
中科院分区:
医学4区
文献类型:
--
作者:
Bae, Seyeon;Oh, Keunhee;Lee, Wang Jae

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Alloferon是一种新型的免疫调节肽,最初从感染昆虫中分离得到。它通过激活NK细胞具有抗病毒和抗肿瘤作用。然而,导致NK细胞活化和抗肿瘤反应的具体机制尚未阐明。在这项研究中,我们证明,alloferon增加NK细胞的杀伤活性的癌细胞通过上调NK细胞激活受体,2B 4的表达。此外,alloferon还能增加NK细胞对癌细胞的IFN-γ和TNF-α的分泌及颗粒胞吐作用。最后,在体内证实了alloferon的抗肿瘤作用,以证明在人-小鼠异种移植模型中有效延缓肿瘤生长。总之,这些结果表明,alloferon通过上调NK活化受体2B 4和增强NK细胞的颗粒胞吐作用而具有抗肿瘤作用。(C)2013 Elsevier GmbH. All rights reserved.
Alloferon is a novel immunomodulatory peptide originally isolated from infected insects. It has antiviral and anti-tumor effects via the activation of NK cells. However, specific mechanisms leading to NK cell activation and anti-tumor responses yet to be clarified. In this study, we demonstrate that alloferon increases killing activity of NK cells to cancer cells via the up-regulation of the expression of NK-activating receptors, 2B4. In addition, the production of IFN-gamma and TNF-alpha and granule exocytosis from NK cells against cancer cell were increased by alloferon. Lastly, the anti-tumor effect of alloferon was confirmed in vivo to demonstrate effective retardation of tumor growth in the human-to-mouse xenograft model. All taken together, these results suggest that alloferon has anti-tumor effects through up-regulation of NK-activating receptor 2B4 and the enhancement of granule exocytosis from NK cells. (C) 2013 Elsevier GmbH. All rights reserved.