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

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 Ni in soluble form (NiCl2) and micro-sized Ni particles (Type 210) 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 barrier function observed by alterations in TEER that 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 (¿GCS). Furthermore, we have demonstrated that the induced effects by Ni compounds can be partially attributed to the increase in Ni ions intracellular levels.

FORTI Efrat;  SALOVARA Susan;  CETIN Yuksel;  BULGHERONI Anna;  TESSADRI Richard;  JENNINGS Paul;  PFALLER Walter;  PRIETO PERAITA Maria Del Pilar; 

2011-02-14

PERGAMON-ELSEVIER SCIENCE LTD

JRC56771

0887-2333,   

https://publications.jrc.ec.europa.eu/repository/handle/JRC56771,   

10.1016/j.tiv.2010.11.013,