In vitro evaluation of the toxicity induced by nickel soluble and particulate forms in human airway epithelial cells

Efrat Forti, Susan Salovaara, Yuksel Cetin, Anna Bulgheroni, Richard Tessadri, Paul Jennings, Walter Pfaller, Pilar Prieto

Research output: Contribution to JournalArticleAcademicpeer-review


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 NiCl(2) 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 (γGCS). 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.

Original languageEnglish
Pages (from-to)454-61
Number of pages8
JournalToxicology in Vitro
Issue number2
Publication statusPublished - Mar 2011


  • Bronchi
  • Cell Survival
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Electric Impedance
  • Epithelial Cells
  • Gene Expression Regulation
  • Humans
  • Nickel
  • Reactive Oxygen Species
  • X-Ray Diffraction
  • Journal Article
  • Research Support, Non-U.S. Gov't


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