Zinc Signals Are Essential for Lipopolysaccharide-Induced Signal Transduction in Monocytes
Zinc Signals Are Essential for Lipopolysaccharide-Induced Signal Transduction in Monocytes
复制标题
DOI：
10.4049/jimmunol.181.9.6491
复制
发表时间：
2008-11-01
影响因子：
4.4
通讯作者：
Rink, Lothar
中科院分区：
文献类型：
--
作者：
Haase, Hajo;Ober-Bloebaum, Julia L.;Rink, Lothar
细胞内钙离子浓度的改变是信号转导的一个组成部分。类似的功能也被假设为其他金属离子，特别是锌（Zn2+），但这仍有待实验验证。Zn2+对多种细胞功能很重要，尤其是在免疫系统中。在其他作用中，它影响促炎细胞因子的形成和分泌，包括tnf - α。在这里，我们证明这些影响是由于生理信号系统涉及细胞内Zn2+信号。细胞内锌离子浓度的增加发生在大肠杆菌、LPS、Pam(3)、CSK(4)、tnf - α或胰岛素刺激人白细胞时，主要发生在单核细胞中。用膜透性锌特异性螯合剂TPEN （N，N，N‘，N’-四akis-（2-吡啶基甲基）乙二胺）螯合这种锌信号，完全阻断脂多糖诱导的包括p38 MAPK、ERK1/2和NF-kappa B的信号通路的激活，并消除促炎细胞因子的释放，包括tnf - α。Zn2+的这种功能不仅限于单核细胞甚至免疫系统，而且似乎是另一种基于细胞内金属离子浓度波动的广义信号系统，与Ca2+平行作用。中华免疫学杂志，2008,18(1):691 - 695。
Cytosolic alterations of calcium ion concentrations are an integral part of signal transduction. Similar functions have been hypothesized for other metal ions, in particular zinc (Zn2+), but this still awaits experimental verification. Zn2+ is important for multiple cellular functions, especially in the immune system. Among other effects, it influences formation and secretion of proinflammatory cytokines, including TNF-alpha. Here we demonstrate that these effects are due to a physiological signaling system involving intracellular Zn2+ signals. An increase of the intracellular zinc ion concentration occurs upon stimulation of human leukocytes with Escherichia coli, LPS, Pam(3)CSK(4), TNF-alpha, or insulin, predominantly in monocytes. Chelating this zinc signal with the membrane permeable zinc-specific chelator TPEN (N,N,N',N'-tetrakis-(2-pyridyl-methyl)ethylenediamine) completely blocks activation of LPS-induced signaling pathways involving p38 MAPK, ERK1/2, and NF-kappa B, and abrogates the release of proinflammatory cytokines, including TNF-alpha. This function of Zn2+ is not limited to monocytes or even the immune system, but seems to be another generalized signaling system based on intracellular fluctuations of metal ion concentrations, acting parallel to Ca2+. The Journal of Immunology, 2008, 181: 6491-6502.