title: Prospective phospholipid markers for skin sensitization prediction in keratinocytes: a phospholipidomic approach.
abstract: Prevalence of skin inflammatory disorders has increased in recent years being estimated that 15-20% of the general population suffers from allergic contact dermatitis (ACD). Currently, the sensitizing potential of chemicals is assessed through animal tests; however growing ethical concerns and actual legislative framework impose the development of new alternative tests. Several genomic and proteomic approaches have already indicated some potential biomarkers, but lipidomic analysis was not so far explored with this purpose. A growing body of data suggests that phospholipids (PLs) play important roles in the modulation of immune responses. Therefore, this work focused in identifying changes in the PLs profile of human keratinocytes (KCs). For that, HaCaT cell line was exposed to two immune stimulators: the strong skin allergen 2,4-dinitrofluorobenzene (DNFB) and the non-allergenic stimulus LPS, and to the irritant benzalkonium chloride (BC), using off line TLC-ESI-MS, HPLC-MS and MS/MS. LPS and DNFB reduced PS class relative content, corroborating with consistent changes observed in its molecular profile. PC profile was also altered by immune stimulators. These findings suggest that PC and PS molecular species may discriminate immunogenic compounds from irritants. Analysis of such alterations may be therefore valuable in a future in vitro test platform for skin sensitization prediction.
authors.affiliation: Faculty of Pharmacy University of Coimbra, 3000-548 Coimbra, Portugal.
authors.forename: Deolinda R
authors.initials: DR
authors.lastname: Santinha
authors.forename: M Luísa
authors.initials: ML
authors.lastname: Dória
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Neves
authors.forename: Elisabete A
authors.initials: EA
authors.lastname: Maciel
authors.forename: João
authors.initials: J
authors.lastname: Martins
authors.forename: Luisa
authors.initials: L
authors.lastname: Helguero
authors.forename: Pedro
authors.initials: P
authors.lastname: Domingues
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Cruz
authors.forename: M Rosário
authors.initials: MR
authors.lastname: Domingues
mesh_terms: D001548:Benzalkonium Compounds / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D019295:Computational Biology; D017449:Dermatitis, Allergic Contact / Q000276:immunology; D004139:Dinitrofluorobenzene / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D010743:Phospholipids / Q000378:metabolism*; D012867:Skin / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
chemical_list: D001548:Benzalkonium Compounds; D015415:Biomarkers; D010743:Phospholipids; D004139:Dinitrofluorobenzene