Zinc at pharmacologic concentrations affects cytokine expression and induces apoptosis of human peripheral blood mononuclear cells
Zinc at pharmacologic concentrations affects cytokine expression and induces apoptosis of human peripheral blood mononuclear cells
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DOI：
10.1016/j.nut.2005.11.009
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发表时间：
2006-05-01
期刊：
影响因子：
4.4
通讯作者：
Cheng, HL
中科院分区：
文献类型：
--
作者：
Chang, KL;Hung, TC;Cheng, HL
目的：本研究检测了不同浓度锌对外周血单个核细胞（PBMCs）凋亡信号通路及免疫功能的影响。
方法：将来自健康受试者的PBMCs在体外采用不同浓度的锌进行处理，以模拟生理（2 - 15 μM）和药理（15 - 100 μM）浓度以及高于100 μM的不同血清状态，并分析其细胞因子和凋亡相关因子的表达情况。
结果：尽管正常生理浓度的锌对PBMCs的免疫功能或凋亡没有影响，但药理浓度（100 μM）或更高浓度会影响这两种功能。锌在浓度高于100 μM时会降低细胞增殖，在至少100 μM浓度时会刺激细胞因子表达。此外，在至少100 μM浓度时，会诱导细胞凋亡，并且半胱天冬酶 - 3以及包括Fas（FasL）和c - fos在内的促凋亡基因的表达增加，它们分别通过受体介导的外源性和线粒体介导的凋亡途径触发细胞凋亡。在至少300 μM浓度时，抗凋亡因子核因子 - κB、Bcl - 2和Bcl - X - L的表达显著降低。
结论：只有在等于或高于血清药理浓度范围时，锌才会刺激健康受试者的PBMCs细胞因子表达并诱导其细胞凋亡。受体介导的外源性途径和线粒体介导的内源性途径参与了这种锌诱导的细胞凋亡。（C）2006爱思唯尔公司。保留所有权利。
Objective: The present study examined the effect of zinc at concentrations of the apoptotic signaling pathway and immune function of peripheral blood mononuclear cells (PBMCs).Methods: PBMCs from healthy subjects were treated in vitro with various zinc concentrations to imitate different serum statuses of physiologic (2 to 15 mu M) and pharmacologic (15 to 100 mu M) concentrations to higher than 100 mu M and analyzed their expressions of cytokines and apoptotically related factors.Results: Although a normal physiologic concentration of zinc had no effect on immunologic function or apoptosis of PBMCs, a pharmacologic concentration (100 mu M) or higher affected both functions. Zinc decreased cell proliferation at concentrations higher than 100 mu M and stimulated cytokine expression at concentrations of at least 100 mu M. Further, at concentrations of at least 100 mu M, apoptosis was induced, and expressions of caspase-3 and proapoptotic genes, including Fas (FasL) and c-fos, which trigger apoptosis through receptor-mediated extrinsic and mitochondrion-mediated apoptotic pathways, respectively, were increased. At concentrations at least 300 mu M, expressions of antiapoptotic factors nuclear factor-kappa B, Bcl-2, and Bcl-X-L were markedly decreased.Conclusions: Zinc stimulates cytokine expression and induces apoptosis of PBMCs from healthy subjects only at concentrations equal to or greater than the serum pharmacologic range. Receptor-mediated extrinsic and mitochondrial-mediated intrinsic pathways are involved in this zinc-induced apoptosis. (C) 2006 Elsevier Inc. All rights reserved.