Nickel induces oxidative burst, NF-κB activation and interleukin-8 production in human neutrophils
Nickel induces oxidative burst, NF-κB activation and interleukin-8 production in human neutrophils
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DOI：
10.1007/s00775-010-0685-3
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发表时间：
2010-11-01
影响因子：
3
通讯作者：
Fernandes, Eduarda
中科院分区：
文献类型：
--
作者：
Freitas, Marisa;Gomes, Ana;Fernandes, Eduarda
许多证据表明，氧化应激和炎症在镍盐的毒性中起着关键作用。考虑到中性粒细胞是炎症过程的积极参与者，即通过产生大量的活性氧，本研究的目的是评估镍对人中性粒细胞氧化爆发的假定激活。通过测定蛋白激酶C（PKC）的活性来评价镍对中性粒细胞NADPH氧化途径的影响。还评价了镍（NF-kappa B）活化和促炎介质白细胞介素（IL）-1 β、IL-6、IL-8和肿瘤坏死因子α的产生。在体内可达到的浓度下，通过激活PKC在体外刺激人嗜中性粒细胞中产生超氧自由基（O-2（-））、过氧化氢（H2 O2）和次氯酸（HOCI）。此外，镍被证明激活NF-κ B B并诱导IL-6的产生。这些观察结果表明，镍对人类中性粒细胞的持续激活可能导致这种金属介导的对人类健康的长期不利影响。
Many lines of evidence have suggested that oxidative stress and inflammation play a pivotal role in the toxicity of nickel salts Considering that neutrophils are active participants in inflammatory processes, namely by producing high amounts of reactive oxygen species, the aim of the present study was to evaluate the putative activation of human neutrophils' oxidative burst by nickel Subsequently, the influence of nickel in the pathways leading to NADPH oxidation in neutrophils was evaluated by measuring protein kinase C (PKC) activation The effects of nickel on neutrophils' nuclear factor kappa B (NF-kappa B) activation and on the production of the proinflammatory mediators interleukin (IL)-1 beta, IL-6, IL-8 and tumour necrosis factor a were also evaluated The results obtained showed that nickel, at concentrations that may be attained in vivo, stimulates the production of superoxide radical (O-2(-)), hydrogen peroxide (H2O2), and hypochlorous acid (HOCI) in human neutrophils in vitro, via activation of PKC In addition, nickel was shown to activate NF-kappa B and to induce the production of IL-8 in these cells These observations indicate that the sustained activation of human neutrophils by nickel may contribute for the long-term adverse effects on human health mediated by this metal