title: Gene expression profiles reveal distinct immunological responses of cobalt and cerium dioxide nanoparticles in two in vitro lung epithelial cell models.
abstract: Fragmentary knowledge exists on cellular signaling responses underlying possible adverse health effects of CoO- and CeO2-nanoparticles (NP)s after inhalation. We aimed to perform a time kinetic study of gene expression profiles induced by these NPs in alveolar A549 and bronchial BEAS-2B epithelial cells, and investigated possible immune system modulation. The kinetics of the cell responses induced by the NPs were different between the lung epithelial models. Both CoO- and CeO2-NP exposure induced mainly downregulation of gene transcription. BEAS-2B cells were found to be more sensitive, as they showed a higher number of differentially expressed transcripts (DET) at a 10-fold lower NP-concentration than A549 cells. Hierarchical clustering of all DET indicated that the transcriptional responses were heterogeneous among the two cell types and two NPs. Between 1% and 14% DET encoding markers involved in immune processes were observed. The transcriptional impact of the metal oxide NPs appeared to be cell-dependent, both at the general and immune response level, whereas each lung epithelial cell model responded differently to the two NP types. Thus, the study provides gene expression markers and immune processes involved in CoO- and CeO2-NP-induced toxicity, and demonstrates the usefulness of comprehensive-omics studies to differentiate between NP responses.
authors.affiliation: Flemish Institute for Technological Research (VITO NV), Environmental Risk and Health Unit, 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 NV), Environmental Risk and Health Unit, Mol, Belgium. Electronic address: sylvie.remy@vito.be.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Remy
authors.affiliation: Institut Català de Nanotecnologia (ICN), Barcelona, Spain. Electronic address: eudald.casals@icn.cat.
authors.forename: Eudald
authors.initials: E
authors.lastname: Casals
authors.affiliation: Flemish Institute for Technological Research (VITO NV), Environmental Risk and Health Unit, Mol, Belgium; Hasselt University, Centre for Environmental Sciences, Diepenbeek, Belgium. Electronic address: patrick.deboever@vito.be.
authors.forename: Patrick
authors.initials: P
authors.lastname: De Boever
authors.affiliation: Flemish Institute for Technological Research (VITO NV), Environmental Risk and Health Unit, Mol, Belgium. Electronic address: hilda.witters@vito.be.
authors.forename: Hilda
authors.initials: H
authors.lastname: Witters
authors.affiliation: Università di Modena e Reggio Emilia, Laboratorio Biomateriali, Modena, Italy. Electronic address: gatti@nanodiagnostics.it.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Gatti
authors.affiliation: Institut Català de Nanotecnologia (ICN), Barcelona, Spain. Electronic address: victor.puntes@icn.cat.
authors.forename: Victor
authors.initials: V
authors.lastname: Puntes
authors.affiliation: Flemish Institute for Technological Research (VITO NV), Environmental Risk and Health Unit, Mol, Belgium. Electronic address: inge.nelissen@vito.be.
authors.forename: Inge
authors.initials: I
authors.lastname: Nelissen
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002563:Cerium / Q000633:toxicity*; D016000:Cluster Analysis; D003035:Cobalt / Q000633:toxicity*; D019295:Computational Biology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D053768:Metal Nanoparticles; D020411:Oligonucleotide Array Sequence Analysis; D010087:Oxides / Q000633:toxicity*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D010087:Oxides; D002563:Cerium; D003035:Cobalt; C030583:ceric oxide; C060728:cobalt oxide
keywords: A549; BEAS-2B; Cerium dioxide; Cobalt oxide; Nanoparticles; Transcriptomics