title: Characterisation of cadmium chloride induced molecular and functional alterations in airway epithelial cells.
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 (CdCl(2)) induced toxicity using Calu-3 cells as an in vitro model of human bronchial epithelial cells. CdCl(2) 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. CdCl(2) 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 CdCl(2) induced barrier damage and stress related genes, while other antioxidants only attenuated CdCl(2) induced HSP70 and HMOX-1 and showed no protective effect on the barrier collapse. These findings indicate that CdCl(2) 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 CdCl(2) induced MT1X, HSP70 and HMOX-1 genes, demonstrates an anti-oxidant effect of NAC in addition to Cd chelation.
authors.affiliation: In-Vitro Methods Unit, European Centre for the Validation of Alternative Methods, Institute for Health and Consumer Protection, European Commission Joint Research Centre, Ispra, Italy.
authors.forename: Efrat
authors.initials: E
authors.lastname: Forti
authors.forename: Anna
authors.initials: A
authors.lastname: Bulgheroni
authors.forename: Yuksel
authors.initials: Y
authors.lastname: Cetin
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.forename: Paul
authors.initials: P
authors.lastname: Jennings
authors.forename: Walter
authors.initials: W
authors.lastname: Pfaller
authors.forename: Pilar
authors.initials: P
authors.lastname: Prieto
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015820:Cadherins / Q000032:analysis / Q000378:metabolism; D019256:Cadmium Chloride / Q000009:adverse effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017097:Electric Impedance; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
chemical_list: D000975:Antioxidants; D015820:Cadherins; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D008668:Metallothionein; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D019256:Cadmium Chloride