Cadmium ions induce monocytic production of tumor necrosis factor-alpha by inhibiting mitogen activated protein kinase dephosphorylation
Cadmium ions induce monocytic production of tumor necrosis factor-alpha by inhibiting mitogen activated protein kinase dephosphorylation
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DOI：
10.1016/j.toxlet.2010.06.010
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发表时间：
2010-10-05
影响因子：
3.5
通讯作者：
Rink, Lothar
中科院分区：
文献类型：
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作者：
Haase, Hajo;Ober-Blobaum, Julia L.;Rink, Lothar
镉离子（Cd 2+）具有致癌性，并在多种生物体中具有细胞毒性作用。除了它的直接细胞毒性。Cd 2+在亚毒性浓度下可作为免疫调节剂。在其他影响中，Cd 2+可以诱导炎症，但这种效应的分子基础还没有得到很好的研究。在这篇手稿中，我们分析了Cd 2+对单核细胞/巨噬细胞的影响，这是促炎细胞因子的有效生产者，发现Cd 2+治疗诱导肿瘤坏死因子（TNF）-α分泌。基于观察到另一种IIb族金属锌（Zn 2+）在这些事件中具有生理作用，我们研究了Cd 2+是否作用于相同的分子靶点。与Zn 2+一样，Cd 2+抑制磷酸酶，从而使丝裂原活化蛋白激酶（MAPK）去磷酸化。因此，用Cd 2+处理细胞导致ERK 1/2和p38 MAPK磷酸化的刺激。此外，Cd 2+诱导的TNF-α从原代人单核细胞的释放被ERK 1/2（U 0126）和p38 MAPK（SB 202190）抑制剂阻断，表明MAPK参与Cd 2+诱导TNF-α。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Cadmium ions (Cd2+) are carcinogenic and have cytotoxic effects in a variety of organisms. In addition to its direct cytotoxicity. Cd2+ acts as an immunomodulator at sub-toxic concentrations. Among other influences Cd2+ can induce inflammation, but the molecular basis for this effect is not well investigated. In this manuscript, we analyze the impact of Cd2+ on monocytes/macrophages, which are potent producers of pro-inflammatory cytokines, finding that Cd2+ treatment induced tumor necrosis factor (TNF)-alpha secretion. Based on the observation that another group IIb metal, zinc (Zn2+), has a physiological role in these events, we investigated if Cd2+ acts on the same molecular targets. Like Zn2+, Cd2+ inhibits phosphatases, and hereby dephosphorylation of mitogen activated protein kinases (MAPK). Consequently, treatment of cells with Cd2+ resulted in stimulation of ERK 1/2 and p38 MAPK phosphorylation. Furthermore, Cd2+-induced release of TNF-alpha from primary human monocytes was blocked by inhibitors for ERK 1/2 (U0126) and p38 MAPK (SB202190), demonstrating that MAPKs are involved in the induction of TNF-alpha by Cd2+. (C) 2010 Elsevier Ireland Ltd. All rights reserved.