Characterisation of Cadmium Chloride Induced Molecular and Functional Alterations in Airway Epithelial Cells

E Forti, A Bulgheroni, Y Cetin, T Hartung, P Jennings, W Pfaller, P Prieto

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Epidemiological studies show that cadmium (Cd) exposure causes pulmonary damage, such as emphysema, pneumonitis, and lung cancer. However, the mechanisms leading to pulmonary toxicity are not yet fully elucidated. The aim of this study was to further investigate cadmium chloride (CdCl2) induced toxicity using Calu-3 cells as an in vitro model of human bronchial epithelial cells. CdCl2 induced effects following either apical or basolateral exposure were evaluated by Neutral Red Uptake (NRU), Trans-Epithelial Electrical Resistance (TEER), and alteration in Metallothionein 1X (MT1X), Heat shock protein 70 (HSP70), and Heme oxygenase 1 (HMOX-1) genes. CdCl2 exposure resulted in a collapse of barrier function and the induction of MT1X, HMOX-1 and HSP70 genes, prior to alterations in cell viability. These effects were more pronounced when the exposure was from the basolateral side. Co-administration of N-Acetylcysteine (NAC) exerted a strong protective effect against CdCl2 induced barrier damage and stress related genes, while other antioxidants only attenuated CdCl2 induced HSP70 and HMOX-1 and showed no protective effect on the barrier collapse. These findings indicate that CdCl2 exposure is likely to impair Calu-3 barrier function at non cytotoxic concentrations by a direct effect on adherens junction proteins. The protective effect of NAC against CdCl2 induced MT1X, HSP70 and HMOX-1 genes, demonstrates an anti-oxidant effect of NAC in addition to Cd chelation.
Original languageEnglish
Pages (from-to)159-168
Number of pages10
JournalCellular Physiology and Biochemistry
Volume25
Issue number1
DOIs
StatePublished - 2010
Externally publishedYes

Keywords

  • Antioxidants
  • Calu-3
  • CdCl2
  • HMOX-1
  • HSP70
  • In vitro
  • Lung toxicity
  • MT1X
  • TEER

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