Interleukin-15 improves cytotoxicity of natural killer cells via up-regulating NKG2D and cytotoxic effector molecule expression as well as STAT1 and ERK1/2 phosphorylation
Interleukin-15 improves cytotoxicity of natural killer cells via up-regulating NKG2D and cytotoxic effector molecule expression as well as STAT1 and ERK1/2 phosphorylation
复制标题
Interleukin-15 通过上调 NKG2D 和细胞毒性效应分子表达以及 STAT1 和 ERK1/2 磷酸化来提高自然杀伤细胞的细胞毒性
DOI：
10.1016/j.cyto.2008.01.003
复制
发表时间：
2008-04-01
期刊：
影响因子：
3.8
通讯作者：
Tian, Zhigang
中科院分区：
文献类型：
--
作者：
Zhang, Cai;Zhang, Jianhua;Tian, Zhigang
NK细胞是先天免疫系统的重要组成部分，提供了对抗感染性病原体和肿瘤的第一道防线。IL-15是负责成熟NK细胞的NK细胞分化、存活和细胞溶解活性的主要生理生长因子。然而，IL-15对NK细胞功能的确切调节机制仍不清楚。本研究旨在探讨IL-15对NK细胞杀伤作用的机制。我们的研究结果表明，IL-15处理增加了NK细胞中NKG 2D的转录和表面表达。NKG 2D或云母阻断减弱了IL-15对NK细胞溶解的上调，表明IL-15对NK细胞溶解的上调作用至少部分依赖于NKG 2D和云母的相互作用。此外，IL-15增强了细胞毒性效应分子（TRAIL和Perform）的表达以及STAT 1和ERK 1/2的磷酸化，这也可能有助于NK细胞溶解。这些结果可能具有治疗意义时，设计细胞因子免疫治疗癌症。(c)2008爱思唯尔有限公司保留所有权利。
NK cells are crucial components of the innate immune system, providing a first line of defense against infectious pathogens and tumors. IL-15 is the major physiologic growth factor responsible for NK cell differentiation, survival and cytolytic activity of mature NK cells. However, the exact regulatory mechanism of IL-15 on NK cell function is still unclear. In this study, we try to investigate the mechanism of IL-15 on NK cytolysis. Our results demonstrate that IL-15 treatment increased NKG2D transcripts and surface expression in NK cells. NKG2D or MICA blockade attenuated the up-regulation of IL-15 on NK cytolysis, demonstrating that the up-regulatory effect of IL-15 on NK cytolysis is at least partly dependent of the interaction of NKG2D and MICA. Furtherfore, IL-15 augmented the expression of cytotoxic effector molecules (TRAIL and Perform) and the phosphorylation of STAT1 and ERK1/2, which may also contribute the NK lysis. These results may have therapeutic implications when designing cytokine immunotherapy against cancer. (c) 2008 Elsevier Ltd. All rights reserved.