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

Arch Toxicol. 2015 Oct;89(10):1759-69. doi: 10.1007/s00204-014-1325-4. Epub 2014 Aug 10.

Abstract

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.

Keywords: Cytokines; Human blood cells; Inflammation; Interleukins; Iron oxide nanoparticles.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylic Resins / chemistry*
  • Cytokines / metabolism*
  • Humans
  • Inflammation / chemically induced*
  • Inflammation / pathology
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Kinase Kinases / metabolism
  • Magnetite Nanoparticles / administration & dosage*
  • Magnetite Nanoparticles / toxicity
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Acrylic Resins
  • Cytokines
  • Magnetite Nanoparticles
  • carbopol 940
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7