title: Identification of PDL-1 as a novel biomarker of sensitizer exposure in dendritic-like cells.
abstract: The development of novel in vitro methods to assess risks of allergic sensitization are essential in reducing animal testing whilst maintaining consumer safety. The main research objectives of this study were to identify novel biomarkers to assess the sensitization predictability of chemicals. Phenotypic and cytokine responses of moDCs and MUTZ-3 cells were investigated following application of contact sensitizers; dinitrochlorobenzene (DNCB), cinnamaldehyde (Cin), eugenol (E), isoeugenol (IE), P-phenylenediamine (PPD) and non-sensitizers; salicyclic acid (SA) and sodium lauryl sulphate (SLS). CD86 was up-regulated on MUTZ-3 cells in response to DNCB, Cin and PPD, however, moDCs only modulated CD86 in response to DNCB and E. PDL-1 (Programmed death receptor ligand-1) proved a promising sensitization biomarker in MUTZ-3 cells where up-regulation occurred in response to DNCB, Cin, IE and PPD. Additionally, moDC-expressed PDL-1 was modulated in response to Cin, IE and E thus demonstrating improved sensitizer predictability when compared with CD86. MCP-1 and RANTES were identified as biomarkers of DNCB exposure but MCP-1 did not show any change in expression above controls for the other sensitizers investigated. However, RANTES was increased in MUTZ-3 cells by both DNCB and Cin. Our findings highlight novel biomarkers which, in MUTZ-3 cells, could be taken forward within a multiple biomarker in vitro assay ensuring strong and reliable predictability.
authors.affiliation: Centre for Research in Biomedicine, Faculty of Health and Life Sciences, University of the West of England, Bristol, United Kingdom.
authors.forename: Emma H
authors.initials: EH
authors.lastname: Williams
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Williams
authors.forename: Julie D
authors.initials: JD
authors.lastname: McLeod
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives / Q000633:toxicity; D000485:Allergens / Q000633:toxicity*; D015703:Antigens, CD / Q000378:metabolism*; D051940:B7-2 Antigen / Q000096:biosynthesis; D060890:B7-H1 Antigen; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D003877:Dermatitis, Contact; D004137:Dinitrochlorobenzene / Q000633:toxicity; D005054:Eugenol / Q000031:analogs & derivatives / Q000633:toxicity; D006801:Humans; D014373:Tuberculin / Q000633:toxicity; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000485:Allergens; D015703:Antigens, CD; D051940:B7-2 Antigen; D060890:B7-H1 Antigen; D015415:Biomarkers; C423236:CD274 protein, human; D004137:Dinitrochlorobenzene; D014373:Tuberculin; D005054:Eugenol; C036643:isoeugenol; D000171:Acrolein; C012843:cinnamaldehyde