title: Nuclear translocation of Nrf2 and expression of antioxidant defence genes in THP-1 cells exposed to carbon nanotubes.
abstract: Carbon nanotubes have a wide range of applications in various industries and their use is likely to rise in the future. Currently, a major concern is that with the increasing use and production of these materials, there may be increased health risks to exposed workers. Long (> 15 microm) straight nanotubes may undergo frustrated phagocytosis which is likely to result in reduced clearance. We examine here the effects of multiwalled carbon nanotubes of different sizes on monocytic THP-1 cells, with regard to their ability to stimulate increased expression of the HO-1 and GST genes and their ability to produce nuclear translocation of the transcription factor, Nrf2, as well as the release of several pro-inflammatory cytokines and mediators of inflammation. Our results suggest that long (50 microm) carbon nanotubes (62.5 microg/ml for 4 hours) produce increased nuclear translocation of Nrf2 and increased HO-1 gene expression compared with shorter entangled nanotubes. There was no increased gene expression for GST. The long nanotubes (NT1) caused increased release of the proinflammatory cytokine IL-1beta, an effect which was diminished by the antioxidant trolox, suggesting a role of oxidative stress in the upregulation of this cytokine. Tentatively, our study suggests that long carbon nanotubes may exert their effect in THP-1 cells in part via an oxidative stress mechanism.
authors.affiliation: School of Life Sciences, Edinburgh Napier University, Edinburgh EH10 5DT, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Brown
authors.forename: Kenneth
authors.initials: K
authors.lastname: Donaldson
authors.forename: Vicki
authors.initials: V
authors.lastname: Stone
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D037742:Nanotubes, Carbon; D027361:Organic Anion Transporters / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D051547:Heme Oxygenase-1; D051267:NF-E2-Related Factor 2; D037742:Nanotubes, Carbon; D027361:Organic Anion Transporters; C495635:NFE2L2 protein, human; C487009:SLCO6A1 protein, human; C496541:HMOX1 protein, human