Archives of Toxicology

, Volume 89, Issue 10, pp 1759–1769 | Cite as

Polyacrylic acid-coated and non-coated iron oxide nanoparticles induce cytokine activation in human blood cells through TAK1, p38 MAPK and JNK pro-inflammatory pathways

  • Diana Couto
  • Marisa Freitas
  • Graça Porto
  • M. Arturo Lopez-Quintela
  • José Rivas
  • Paulo Freitas
  • Félix CarvalhoEmail author
  • Eduarda FernandesEmail author


Iron oxide nanoparticles (ION) can have a wide scope of applications in biomedicine, namely in magnetic resonance imaging, tissue repair, drug delivery, hyperthermia, transfection, tissue soldering, and as antimicrobial agents. The safety of these nanoparticles, however, is not completely established, namely concerning their effect on immune system and inflammatory pathways. The aim of this study was to evaluate the in vitro effect of polyacrylic acid (PAA)-coated ION and non-coated ION on the production of six cytokines [interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), interferon gamma (IFN-γ) and interleukin 10 (IL-10)] by human peripheral blood cells, and to determine the inflammatory pathways involved in this production. The obtained results showed that PAA-coated and non-coated ION were able to induce all the tested cytokines and that activation of transforming growth factor beta (TGF-β)-activated kinase (TAK1), p38 mitogen-activated protein kinases (p38 MAPK) and c-Jun N-terminal kinases (JNK) were involved in this effect.


Iron oxide nanoparticles Human blood cells Inflammation Cytokines Interleukins 



Diana Couto acknowledges the Fundação para a Ciência e Tecnologia (FCT) financial support for the PhD grant (SFRH/BD/72856/2010) and Marisa Freitas for her Pos-doc grant (SFRH/BPD/76909/2011), in the ambit of “POPH–QREN–Tipologia 4.1–Formação Avançada” co-sponsored by FSE and national funds of MCTES. The authors greatly acknowledge the financial support given by Reitoria da Universidade do Porto and Santander Totta for Projectos IJUP 2011.

Conflict of interest

Authors declare no conflicts of interest concerning the present study.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Diana Couto
    • 1
  • Marisa Freitas
    • 1
  • Graça Porto
    • 2
  • M. Arturo Lopez-Quintela
    • 3
  • José Rivas
    • 4
  • Paulo Freitas
    • 4
  • Félix Carvalho
    • 5
    Email author
  • Eduarda Fernandes
    • 1
    Email author
  1. 1.REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of PharmacyUniversity of PortoPortoPortugal
  2. 2.Service of Clinical HematologySanto António HospitalPortoPortugal
  3. 3.Laboratory of Nanotechnology and Magnetism, Institute of Technological ResearchUniversity of Santiago de CompostelaSantiago de CompostelaSpain
  4. 4.International Iberian Nanotechnology LaboratoryBragaPortugal
  5. 5.REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of PharmacyUniversity of PortoPortoPortugal

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