title: Phospholipidomic Profile Variation on THP-1 Cells Exposed to Skin or Respiratory Sensitizers and Respiratory Irritant.
abstract: Occupational exposure to low molecular weight reactive chemicals often leads to development of allergic reactions such as allergic contact dermatitis and respiratory allergies. Further insights into the interaction of these chemicals with physiopathological relevant cellular models might provide the foundations for novel non-animal approaches to safety assessment. In this work we used the human THP-1 cell line to determine phospholipidome changes induced by the skin sensitizer 1-fluoro-2,4-dinitrobenzene (DNFB), the respiratory allergen hexamethylene diisocyanate (HDI), and the irritant methyl salicylate (MESA). We detected that these chemicals differently induce lipid peroxidation and modulate THP-1 IL-1β, IL-12B, IL-8, CD86, and HMOX1 transcription. Decreased phosphatidylethanolamine content was detected in cells exposed to MESA, while profound alterations in the relative abundance of cardiolipin species were observed in cells exposed to DNFB. All chemicals tested induced a decrease in the relative abundance of plasmanyl phosphatidylcholine species PC (O-16:0e/18:1) and phosphatidylinositol species PI (34:1), while increasing PI (38:4). An increased abundance of oleic acid was observed in the phospholipids of cells exposed to DNFB while a decreased abundance of palmitic acid was detected in cells treated with MESA or DNFB. We conclude that both specific and common alterations at phospholipidome levels are triggered by the different chemicals, while not allowing a complete distinction between them using a Canonical Analysis of Principal Coordinates (CAP). The common effects observed at phospholipids level with all the chemicals tested might be related to unspecific cell cytotoxic mechanisms that nevertheless may contribute to the elicitation of specific immune responses. J. Cell. Physiol. 231: 2639-2651, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.|Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal.
authors.forename: João D
authors.initials: JD
authors.lastname: Martins
authors.affiliation: Department of Chemistry, Mass Spectrometry Centre, University of Aveiro, Aveiro, Portugal.|Departament of Biology and CESAM, University of Aveiro, Campus Universitário de Santiago, Aveiro, Portugal.
authors.forename: Elisabete A
authors.initials: EA
authors.lastname: Maciel
authors.affiliation: Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Silva
authors.affiliation: Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Ferreira
authors.affiliation: Departament of Biology and CESAM, University of Aveiro, Campus Universitário de Santiago, Aveiro, Portugal.
authors.forename: Fernando
authors.initials: F
authors.lastname: Ricardo
authors.affiliation: Department of Chemistry, Mass Spectrometry Centre, University of Aveiro, Aveiro, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Domingues
authors.affiliation: Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.|Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal.|Department of Chemistry, Mass Spectrometry Centre, University of Aveiro, Aveiro, Portugal.
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Neves
authors.affiliation: Department of Chemistry, Mass Spectrometry Centre, University of Aveiro, Aveiro, Portugal.
authors.forename: Maria Rosário M
authors.initials: MR
authors.lastname: Domingues
authors.affiliation: Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.|Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Cruz
mesh_terms: D002460:Cell Line; D002853:Chromatography, Liquid; D002855:Chromatography, Thin Layer; D004139:Dinitrofluorobenzene / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007509:Irritants / Q000494:pharmacology*; D017953:Isocyanates / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism; D013058:Mass Spectrometry; D010743:Phospholipids / Q000378:metabolism*; D025341:Principal Component Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012119:Respiration / Q000187:drug effects*; D012459:Salicylates / Q000494:pharmacology; D012867:Skin / Q000187:drug effects*
chemical_list: D005227:Fatty Acids; D007509:Irritants; D017953:Isocyanates; D008054:Lipid Peroxides; D010743:Phospholipids; D012333:RNA, Messenger; D012459:Salicylates; C015262:1,6-hexamethylene diisocyanate; D004139:Dinitrofluorobenzene; C033069:methyl salicylate