Title
Gene expressions changes in bronchial epithelial cells : markers for respiratory sensitizers and exploration of the NRF2 pathway Gene expressions changes in bronchial epithelial cells : markers for respiratory sensitizers and exploration of the NRF2 pathway
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
Oxford ,
Subject
Pharmacology. Therapy
Source (journal)
Toxicology in vitro. - Oxford
Volume/pages
28(2014) :2 , p. 209-217
ISSN
0887-2333
ISI
000331029200009
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
For the classification of respiratory sensitizing chemicals, no validated in vivo nor in vitro tests are currently available. In this study, we evaluated whether respiratory sensitizers trigger specific signals in human bronchial epithelial (BEAS-2B) cells at the level of the transcriptome. The cells were exposed during 6, 10, and 24 h to 4 respiratory sensitizers and 6 non-respiratory sensitizers (3 skin sensitizers and 3 respiratory irritants) at a concentration inducing 20% cell viability loss after 24 h. Changes in gene expression were evaluated using Agilent Whole Human Genome 4 x 44 K oligonucleotide arrays. A limited number of 11 transcripts could be identified as potential biomarkers to identify respiratory sensitizers. Three of these transcripts are associated to immune system processes (HSPA5, UPP1, and SEPRINEI). In addition, the transcriptome was screened for transcripts that are differentially expressed compared to vehicle control for each chemical. The results show that the NRF2-mediated oxidative stress response is activated in the cell line after stimulation with all of the chemicals that were selected in our study, and that - at the level of gene expression - this pathway shows no potential to discriminate between any of the three compound groups: respiratory sensitizers, skin sensitizers, or electrophilic respiratory irritants. (C) 2013 Elsevier Ltd. All rights reserved.
E-info
https://repository.uantwerpen.be/docman/iruaauth/cdf151/d017160.pdf
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