Nickel induces oxidative burst, NF-κB activation and interleukin-8 production in human neutrophils |
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Authors: | Marisa Freitas Ana Gomes Graça Porto Eduarda Fernandes |
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Institution: | 1. REQUIMTE, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, 164, 4099-030, Porto, Portugal 2. Servi?o de Hematologia Clínica, Hospital Geral de Santo António, Largo Professor Abel Salazar, 4099-001, Porto, Portugal
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Abstract: | 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 κB (NF-κB) activation
and on the production of the proinflammatory mediators interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor α were also
evaluated. The results obtained showed that nickel, at concentrations that may be attained in vivo, stimulates the production of superoxide radical (O2
·−), hydrogen peroxide (H2O2), and hypochlorous acid (HOCl) in human neutrophils in vitro, via activation of PKC. In addition, nickel was shown to activate
NF-κB 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. |
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