JBIC Journal of Biological Inorganic Chemistry

, Volume 15, Issue 8, pp 1275–1283

Nickel induces oxidative burst, NF-κB activation and interleukin-8 production in human neutrophils

  • Marisa Freitas
  • Ana Gomes
  • Graça Porto
  • Eduarda Fernandes
Original Paper

DOI: 10.1007/s00775-010-0685-3

Cite this article as:
Freitas, M., Gomes, A., Porto, G. et al. J Biol Inorg Chem (2010) 15: 1275. doi:10.1007/s00775-010-0685-3

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.

Keywords

Human neutrophilsOxidative burstNickelProtein kinase CNuclear factor κB

Abbreviations

ABAH

4-Aminobenzoyl hydrazide

APF

2-[6-(4′-Amino)phenoxy-3H-xanthen-3-on-9-yl]benzoic acid

DPI

Diphenyleneiodonium chloride

EGTA

Ethylene glycol bis(2-aminoethyl ether)-N,N,N′,N′-tetraacetic acid

Gö6983

3-[1-[3-(Dimethylamino)propyl]-5-methoxy-1H-indol-3-yl]-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione

HEPES

N-(2-Hydroxyethyl)piperazine-N′-ethanesulfonic acid

HRP

Horseradish peroxidase

IKK

IκB kinase

IL

Interleukin

l-NAME

N-Nitro-l-arginine methyl ester

MAPK

Mitogen-activated protein kinase

MPO

Myeloperoxidase

NF-κB

Nuclear factor κB

NOS

Nitric oxide synthase

PKC

Protein kinase C

PMSF

Phenylmethanesulfonyl fluoride

RNS

Reactive nitrogen species

ROS

Reactive oxygen species

TNF-α

Tumour necrosis factor α

Tris

Tris(hydroxymethyl)aminomethane

Copyright information

© SBIC 2010

Authors and Affiliations

  • Marisa Freitas
    • 1
  • Ana Gomes
    • 1
  • Graça Porto
    • 2
  • Eduarda Fernandes
    • 1
  1. 1.REQUIMTE, Departamento de Química, Faculdade de FarmáciaUniversidade do PortoPortoPortugal
  2. 2.Serviço de Hematologia ClínicaHospital Geral de Santo António, Largo Professor Abel SalazarPortoPortugal