TY - JOUR
T1 - Immunotoxicity of organophosphate flame retardants TPHP and TDCIPP on murine dendritic cells in vitro
AU - Canbaz, Derya
AU - Logiantara, Adrian
AU - van Ree, Ronald
AU - van Rijt, Leonie S.
PY - 2017
Y1 - 2017
N2 - 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
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 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
U2 - https://doi.org/10.1016/j.chemosphere.2017.02.149
DO - https://doi.org/10.1016/j.chemosphere.2017.02.149
M3 - Article
C2 - 28282624
SN - 0045-6535
VL - 177
SP - 56
EP - 64
JO - Chemosphere
JF - Chemosphere
ER -