PMID- 28282624 OWN - NLM STAT- MEDLINE DCOM- 20170531 LR - 20181202 IS - 1879-1298 (Electronic) IS - 0045-6535 (Linking) VI - 177 DP - 2017 Jun TI - Immunotoxicity of organophosphate flame retardants TPHP and TDCIPP on murine dendritic cells in vitro. PG - 56-64 LID - S0045-6535(17)30338-7 [pii] LID - 10.1016/j.chemosphere.2017.02.149 [doi] AB - 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 muM) 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 muM 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. CI - Copyright (c) 2017 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Canbaz, Derya AU - Canbaz D AD - Dept of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, The Netherlands. FAU - Logiantara, Adrian AU - Logiantara A AD - Dept of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, The Netherlands. FAU - van Ree, Ronald AU - van Ree R AD - 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. FAU - van Rijt, Leonie S AU - van Rijt LS AD - Dept of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, The Netherlands. Electronic address: l.s.vanrijt@amc.uva.nl. LA - eng PT - Journal Article DEP - 20170228 PL - England TA - Chemosphere JT - Chemosphere JID - 0320657 RN - 0 (Allergens) RN - 0 (Antioxidants) RN - 0 (Flame Retardants) RN - 0 (Halogenated Diphenyl Ethers) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Interleukin-6) RN - 0 (Organophosphates) RN - 0 (Phosphates) RN - YZE19Z66EA (triphenyl phosphate) SB - IM MH - Allergens/adverse effects MH - Animals MH - Antioxidants/chemistry MH - Bone Marrow Cells/drug effects MH - Dendritic Cells/drug effects MH - Dose-Response Relationship, Drug MH - Female MH - Flame Retardants/*toxicity MH - Halogenated Diphenyl Ethers/*toxicity MH - Histocompatibility Antigens Class II/chemistry MH - Inflammation MH - Interleukin-6/chemistry MH - Mice MH - Mice, Inbred BALB C MH - Organophosphates/*toxicity MH - Oxidative Stress MH - Phenotype MH - Phosphates/toxicity MH - Pyroglyphidae OTO - NOTNLM OT - Allergy OT - Dendritic cells OT - House dust mite OT - Phosphorus flame retardants EDAT- 2017/03/11 06:00 MHDA- 2017/06/01 06:00 CRDT- 2017/03/11 06:00 PHST- 2016/11/14 00:00 [received] PHST- 2017/02/01 00:00 [revised] PHST- 2017/02/27 00:00 [accepted] PHST- 2017/03/11 06:00 [pubmed] PHST- 2017/06/01 06:00 [medline] PHST- 2017/03/11 06:00 [entrez] AID - S0045-6535(17)30338-7 [pii] AID - 10.1016/j.chemosphere.2017.02.149 [doi] PST - ppublish SO - Chemosphere. 2017 Jun;177:56-64. doi: 10.1016/j.chemosphere.2017.02.149. Epub 2017 Feb 28.