title: Gene profiles of THP-1 macrophages after in vitro exposure to respiratory (non-)sensitizing chemicals: identification of discriminating genetic markers and pathway analysis.
abstract: It is recognized that respiratory sensitization is a hazard of high concern. Despite international regulatory requirements there is no established protocol for the identification of chemical respiratory sensitizers. New tests should be based on mechanistic understanding and should be preferentially restricted to in vitro assays. The major goal of this study was to investigate the genetic response of human THP-1 macrophages after contact with respiratory (non-)sensitizers, and to identify genes that are able to discriminate between both groups. THP-1 macrophages were exposed during different time points to 3 respiratory sensitizers, 2 irritants, and 1 skin sensitizer. Gene expression changes were evaluated using Agilent Whole Human Genome arrays. Fisher Linear Discriminant Analysis was used to obtain a ranking of genes that reflects their potential to discriminate between respiratory (non-)sensitizing chemicals. Among the 20 most discriminating genes which were categorized into molecular and biological Gene Ontology (GO) terms, EIF4E, PDGFRB, SEMA7A, and ZFP36L2 could be associated with respiratory sensitization. When categorizing the top-1000 genes into biological GO terms, 24 genes were associated with immune function. Using a pathway analysis tool, platelet-derived growth factor signaling was observed to be activated in THP-1 macrophages in the context of respiratory sensitization.
authors.affiliation: Unit Environmental Risk and Health, Flemish Institute for Technological Research (VITO NV), Boeretang 200, 2400 Mol, Belgium. sandra.verstraelen@vito.be
authors.forename: Sandra
authors.initials: S
authors.lastname: Verstraelen
authors.forename: Inge
authors.initials: I
authors.lastname: Nelissen
authors.forename: Jef
authors.initials: J
authors.lastname: Hooyberghs
authors.forename: Hilda
authors.initials: H
authors.lastname: Witters
authors.forename: Greet
authors.initials: G
authors.lastname: Schoeters
authors.forename: Paul
authors.initials: P
authors.lastname: Van Cauwenberge
authors.forename: Rosette
authors.initials: R
authors.lastname: Van Den Heuvel
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000633:toxicity*; D002460:Cell Line; D016002:Discriminant Analysis; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D015894:Genome, Human; D006801:Humans; D007509:Irritants / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D000485:Allergens; D007509:Irritants; D010982:Platelet-Derived Growth Factor