title: 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.
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.
authors.affiliation: REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Diana
authors.initials: D
authors.lastname: Couto
authors.affiliation: REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Marisa
authors.initials: M
authors.lastname: Freitas
authors.affiliation: Service of Clinical Hematology, Santo António Hospital, Porto, Portugal.
authors.forename: Graça
authors.initials: G
authors.lastname: Porto
authors.affiliation: Laboratory of Nanotechnology and Magnetism, Institute of Technological Research, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: M Arturo
authors.initials: MA
authors.lastname: Lopez-Quintela
authors.affiliation: International Iberian Nanotechnology Laboratory, Braga, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Rivas
authors.affiliation: International Iberian Nanotechnology Laboratory, Braga, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Freitas
authors.affiliation: REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal. felixdc@ff.up.pt.
authors.forename: Félix
authors.initials: F
authors.lastname: Carvalho
authors.affiliation: REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal. egracas@ff.up.pt.
authors.forename: Eduarda
authors.initials: E
authors.lastname: Fernandes
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000633:toxicity; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D000180:Acrylic Resins; D016207:Cytokines; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D058185:Magnetite Nanoparticles; D048051:p38 Mitogen-Activated Protein Kinases; D000099151:MAP Kinase Kinase Kinase 7; C006903:carbopol 940
keywords: Cytokines; Human blood cells; Inflammation; Interleukins; Iron oxide nanoparticles