期刊
TOXICOLOGY IN VITRO
卷 25, 期 2, 页码 454-461出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2010.11.013
关键词
Airway epithelial cells; NiCl(2); Ni particles; In vitro; Barrier integrity; Oxidative stress
类别
资金
- Marie Curie Research Training Network Pulmo-Net [MRTN-CT-2004-512229]
Epidemiological studies show that exposure to nickel (Ni) compounds is associated with a variety of pulmonary adverse health effects, such as lung inflammation, fibrosis, emphysema and tumours. However, the mechanisms leading to pulmonary toxicity are not yet fully elucidated. In the current study we used Calu-3, a well differentiated human bronchial cell line, to investigate in vitro the effect of Ni in soluble form (NiCl(2)) and in the form of micro-sized Ni particles on the airway epithelium. For this purpose, we evaluated the effect of Ni compounds on the epithelial barrier integrity by monitoring the transepithelial electrical resistance (TEER) and on oxidative stress pathways by measuring reactive oxygen species (ROS) formation and induction of stress-inducible genes. Our results showed that exposure to NiCl2 and Ni particles resulted in a disruption of the epithelial barrier function observed by alterations in TEER, which occurred prior to the decrease in cell viability. Moreover. Ni compounds induced oxidative stress associated with ROS formation and up-regulation of the stress-inducible genes, Metallothionein 1X (MT1X), Heat shock protein 70 (HSP70), Heme oxygenase-1 (HMOX-1), and gamma-glutamylcysteine synthetase (gamma GCS). Furthermore, we have demonstrated that the induced effects by Ni compounds can be partially attributed to the increase in Ni ions (Ni(2+)) intracellular levels. (C) 2010 Elsevier Ltd. All rights reserved.
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