期刊
TOXICOLOGY IN VITRO
卷 24, 期 3, 页码 1002-1008出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2009.12.007
关键词
Human; Neutrophils; Nanoparticles; TiO2; Cytokines; Signal transduction
类别
资金
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- Environmental Health Research Network (RRSE) from Fonds de la Recherche en Sante du Quebec (FRSQ)
This paper describes the in vitro effects of titanium dioxide (TiO2) nanoparticles (NPs) upon human neutrophils. Kinetic experiments revealed no cell necrosis after 24 h of treatment with TiO2 (0-100 mg/ml). In contrast, TiO2-induced change in cellular morphology in a concentration-dependent manner in neutrophils over time, indicating its potential to activate these cells. To further support this, we demonstrated that TiO2 markedly and rapidly induced tyrosine phosphorylation events, including phosphorylation of two key enzymes, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases-1/2 (Erk-1/2). We also determined the effects of TiO2 on two neutrophil functions requiring a longer exposure period between NPs and cells: apoptosis and cytokine production. Interestingly, at concentrations >= 20 mu g/ml, TiO2 inhibited neutrophil apoptosis in a concentration-dependent manner after 24 h of treatment. Supernatants from TiO2-induced neutrophils were harvested after 24 h and tested for the presence of 36 different analytes (cytokines, chemokines) using an antibody array assay. TiO2 treatment increased production of 13 (36%) analytes, including IL-8, which exhibited the greatest increase (similar to 16 x control cell levels). The increased production of IL-8 was confirmed by ELISA. We conclude that TiO2 exerts important neutrophil agonistic properties in vitro. (C) 2009 Elsevier Ltd. All rights reserved.
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