title: Cerium dioxide nanoparticles do not modulate the lipopolysaccharide-induced inflammatory response in human monocytes.
abstract: BACKGROUND
  Cerium dioxide (CeO(2)) nanoparticles have potential therapeutic applications and are widely used for industrial purposes. However, the effects of these nanoparticles on primary human cells are largely unknown. The ability of nanoparticles to exacerbate pre-existing inflammatory disorders is not well documented for engineered nanoparticles, and is certainly lacking for CeO(2) nanoparticles. We investigated the inflammation-modulating effects of CeO(2) nanoparticles at noncytotoxic concentrations in human peripheral blood monocytes.
  
  
  METHODS
  CD14(+) cells were isolated from peripheral blood samples of human volunteers. Cells were exposed to either 0.5 or 1 μg/mL of CeO(2) nanoparticles over a period of 24 or 48 hours with or without lipopolysaccharide (10 ng/mL) prestimulation. Modulation of the inflammatory response was studied by measuring secreted tumor necrosis factor-alpha, interleukin-1beta, macrophage chemotactic protein-1, interferon-gamma, and interferon gamma-induced protein 10.
  
  
  RESULTS
  CeO(2) nanoparticle suspensions were thoroughly characterized using dynamic light scattering analysis (194 nm hydrodynamic diameter), zeta potential analysis (-14 mV), and transmission electron microscopy (irregular-shaped particles). Transmission electron microscopy of CD14(+) cells exposed to CeO(2) nanoparticles revealed that these nanoparticles were efficiently internalized by monocytes and were found either in vesicles or free in the cytoplasm. However, no significant differences in secreted cytokine profiles were observed between CeO(2) nanoparticle-treated cells and control cells at noncytotoxic doses. No significant effects of CeO(2) nanoparticle exposure subsequent to lipopolysaccharide priming was observed on cytokine secretion. Moreover, no significant difference in lipopolysaccharide-induced cytokine production was observed after exposure to CeO(2) nanoparticles followed by lipopolysaccharide exposure.
  
  
  CONCLUSIONS
  CeO(2) nanoparticles at noncytotoxic concentrations neither modulate pre-existing inflammation nor prime for subsequent exposure to lipopolysaccharides in human monocytes from healthy subjects.
authors.affiliation: Clinical Research Unit, National Institute of Environmental Health Sciences/National Institute of Health, Research Triangle Park, Durham, NC 27709, USA. salik.hussain@nih.gov
authors.forename: Salik
authors.initials: S
authors.lastname: Hussain
authors.forename: Faris
authors.initials: F
authors.lastname: Al-Nsour
authors.forename: Annette B
authors.initials: AB
authors.lastname: Rice
authors.forename: Jamie
authors.initials: J
authors.lastname: Marshburn
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Ji
authors.forename: Jeffery I
authors.initials: JI
authors.lastname: Zink
authors.forename: Brenda
authors.initials: B
authors.lastname: Yingling
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Walker
authors.forename: Stavros
authors.initials: S
authors.lastname: Garantziotis
mesh_terms: D000704:Analysis of Variance; D002470:Cell Survival; D002478:Cells, Cultured; D002563:Cerium / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000009:adverse effects; D053768:Metal Nanoparticles / Q000737:chemistry*; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D050997:Nanomedicine; D010587:Phagocytosis
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D002563:Cerium; C030583:ceric oxide