title: Immunotoxicity of organophosphate flame retardants TPHP and TDCIPP on murine dendritic cells in vitro.
abstract: Organophosphate flame retardants (PFRs) are commonly used as alternatives for the banned polybrominated diphenyl ethers (PBDEs) and are ubiquitously detected in indoor dust. PFRs can be potentially hazardous to respiratory health via the inhalation of house dust. Dendritic cells (DCs) are crucial in the immunological defense against pathogens in the airways. In respiratory allergy however, an aberrant immune response is induced against innocuous proteins, like house dust mite allergens. In this study, we examined whether exposure to PFRs Triphenylphosphate (TPHP) and Tris(1,3-dichloroisopropyl) phosphate (TDCIPP) affected activation/maturation of DCs at steady state and during exposure to house dust mite allergens (HDM). Bone marrow-derived dendritic cells (BMDCs) were exposed to a concentration range of each PFR (0.1-100 μM) with or without HDM in vitro to analyze the effect on the expression of major histocompatibility complex class II (MHCII), co-stimulatory molecules and cytokine production. Concentrations of TPHP and TDCIPP of ≥50 μM were cytotoxic to BMDCs. At these cytotoxic concentrations, TPHP exposure induced an activated phenotype in steady state DCs, while HDM exposed DCs acquired a tolerogenic phenotype. In contrast, TDCIPP exposure had no effect at steady state DCs but suppressed the expression of MHCII, costimulatory molecules, and the IL-6 production in HDM exposed DCs. The cytotoxic concentrations induced the anti-oxidant enzyme hemeoxigenase-1, which is a marker for oxidative stress. These results demonstrate that PFRs can be immunotoxic for DCs and suggest the necessity to evaluate the effects on the immune system on a cellular level during the risk assessment of these alternative flame retardants.
authors.affiliation: Dept of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, The Netherlands.
authors.forename: Derya
authors.initials: D
authors.lastname: Canbaz
authors.affiliation: Dept of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, The Netherlands.
authors.forename: Adrian
authors.initials: A
authors.lastname: Logiantara
authors.affiliation: Dept of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, The Netherlands; Dept of Otorhinolaryngology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: van Ree
authors.affiliation: Dept of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, The Netherlands. Electronic address: l.s.vanrijt@amc.uva.nl.
authors.forename: Leonie S
authors.initials: LS
authors.lastname: van Rijt
mesh_terms: D000485:Allergens / Q000009:adverse effects; D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D001854:Bone Marrow Cells / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005411:Flame Retardants / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry; D007249:Inflammation; D015850:Interleukin-6 / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D010755:Organophosphates / Q000633:toxicity*; D018384:Oxidative Stress; D010641:Phenotype; D010710:Phosphates / Q000633:toxicity; D039981:Pyroglyphidae
chemical_list: D000485:Allergens; D000975:Antioxidants; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6; D010755:Organophosphates; D010710:Phosphates; C005445:triphenyl phosphate
keywords: Allergy; Dendritic cells; House dust mite; Phosphorus flame retardants