Nickel induces oxidative burst, NF-κB activation and interleukin-8 production in human neutrophils.
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 (O(2)(·-)), hydrogen peroxide (H(2)O(2)), 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.
Freitas
Marisa
M
REQUIMTE, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, 164, 4099-030, Porto, Portugal.
Gomes
Ana
A
Porto
Graça
G
Fernandes
Eduarda
E
D002499:Centrifugation, Density Gradient; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D009532:Nickel / Q000494:pharmacology*; D011493:Protein Kinase C / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology*; D016897:Respiratory Burst / Q000187:drug effects* / Q000276:immunology
D016209:Interleukin-8; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D009532:Nickel; D011493:Protein Kinase C