title: Gene expressions changes in bronchial epithelial cells: markers for respiratory sensitizers and exploration of the NRF2 pathway.
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 24h 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 24h. Changes in gene expression were evaluated using Agilent Whole Human Genome 4×44K 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 SEPRINE1). 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.
authors.affiliation: Flemish Institute for Technological Research (VITO), Unit Environmental Risk and Health, Boeretang 200, Mol, Belgium; Department of Biomedical Sciences, Antwerp University, Universiteitsplein 1, Antwerp, Belgium. Electronic address: sylvie.remy@vito.be.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Remy
authors.affiliation: Flemish Institute for Technological Research (VITO), Unit Environmental Risk and Health, Boeretang 200, Mol, Belgium. Electronic address: sandra.verstraelen@vito.be.
authors.forename: Sandra
authors.initials: S
authors.lastname: Verstraelen
authors.affiliation: Flemish Institute for Technological Research (VITO), Unit Environmental Risk and Health, Boeretang 200, Mol, Belgium. Electronic address: rosette.vandenheuvel@vito.be.
authors.forename: Rosette
authors.initials: R
authors.lastname: Van Den Heuvel
authors.affiliation: Flemish Institute for Technological Research (VITO), Unit Environmental Risk and Health, Boeretang 200, Mol, Belgium. Electronic address: inge.nelissen@vito.be.
authors.forename: Inge
authors.initials: I
authors.lastname: Nelissen
authors.affiliation: Flemish Institute for Technological Research (VITO), Unit Environmental Risk and Health, Boeretang 200, Mol, Belgium. Electronic address: nathalie.lambrechts@vito.be.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lambrechts
authors.affiliation: Flemish Institute for Technological Research (VITO), Unit Environmental Risk and Health, Boeretang 200, Mol, Belgium; Theoretical Physics, Hasselt University, Campus Diepenbeek, Agoralaan - Building D, Diepenbeek, Belgium. Electronic address: jef.hooyberghs@vito.be.
authors.forename: Jef
authors.initials: J
authors.lastname: Hooyberghs
authors.affiliation: Flemish Institute for Technological Research (VITO), Unit Environmental Risk and Health, Boeretang 200, Mol, Belgium; Department of Biomedical Sciences, Antwerp University, Universiteitsplein 1, Antwerp, Belgium; Department of Environmental Medicine, University of Southern Denmark, Winslowsparken 17, Odense, Denmark. Electronic address: greet.schoeters@vito.be.
authors.forename: Greet
authors.initials: G
authors.lastname: Schoeters
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D003627:Data Interpretation, Statistical; D000091342:Endoplasmic Reticulum Chaperone BiP; D004847:Epithelial Cells / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology*; D005819:Genetic Markers / Q000235:genetics; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D006824:Hybridization, Genetic; D007509:Irritants / Q000633:toxicity; D046228:Microarray Analysis; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D005819:Genetic Markers; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D007509:Irritants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D012313:RNA
keywords: BEAS-2B cell line; Gene expression markers; In vitro; Respiratory sensitization; Transcriptomics