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Peer-reviewedCC BY-NC-ND 4.0Environmental Pollution

Repeated exposure to polyethylene microplastic mixtures containing PFAS and bisphenols activates THP-1 macrophages with inflammatory features

Abstract

Microplastics (MPs) are pervasive in the environment and are toxic due to the nature of their polymers and associated additives, such as bisphenols (BPs) and per- and polyfluoroalkyl substances (PFAS). Nonetheless, there is a scarcity of in vitro studies investigating the toxicity of MPs combined with these additives and deciphering the underlying mechanisms in the context of recurrent exposures, which more accurately reflect human contamination. The objective of this study is to assess the differential toxic impacts of polyethylene microplastics (PE-MPs, 100 μg/mL) and a mixture of additives (i.e., AddMix containing 10 μM of BPA, BPS, PFOS, and PFOA) on naive THP-1 macrophages during unique or three repeated exposures over five days. Scanning electron and Raman microscopy images indicated an effective internalization of PE-MPs by macrophages after 30 min and 24 h of exposure. Three repeated exposures of THP-1 macrophages to PE-MPs and PE-MPs + AddMix over five days increased mitochondrial ROS production by 19 % and 13 %, respectively, and led to a more pronounced glycolytic phenotype, associated with the enhanced secretion of the pro-inflammatory cytokine IL-1β by 38 % with PE-MPs. Analysis of transcriptomic data revealed that PE-MPs and/or AddMix significantly enhanced the expression of genes primarily related to inflammation and modulation of lipid metabolism pathways. Our work highlights that MPs mixtures with additives, particularly upon repeated exposure, are recognized by macrophages as activation signals, leading to stimulation of inflammatory pathways, which require further investigation to be fully deciphered.

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BibTeX
@article{gaillard2026repeated,
  title = {{Repeated exposure to polyethylene microplastic mixtures containing PFAS and bisphenols activates THP-1 macrophages with inflammatory features}},
  author = {Lucas Gaillard and Léo Sportes-Milot and Kloé Debizet and Arnaud Tête and Bruno Saubamea and Doumet Georges Helou and Stéphanie Devineau and Xavier Coumoul and Étienne Blanc and Sylvie Bortoli and Karine Andréau},
  journal = {Environmental Pollution},
  year = {2026},
  month = oct,
  doi = {10.1016/j.envpol.2026.127906},
  url = {https://hal.science/hal-05752155v1},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Repeated exposure to polyethylene microplastic mixtures containing PFAS and bisphenols activates THP-1 macrophages with inflammatory features
AU  - Lucas Gaillard
AU  - Léo Sportes-Milot
AU  - Kloé Debizet
AU  - Arnaud Tête
AU  - Bruno Saubamea
AU  - Doumet Georges Helou
AU  - Stéphanie Devineau
AU  - Xavier Coumoul
AU  - Étienne Blanc
AU  - Sylvie Bortoli
AU  - Karine Andréau
PY  - 2026
DA  - 2026/10/19
JO  - Environmental Pollution
DO  - 10.1016/j.envpol.2026.127906
UR  - https://hal.science/hal-05752155v1
AB  - Microplastics (MPs) are pervasive in the environment and are toxic due to the nature of their polymers and associated additives, such as bisphenols (BPs) and per- and polyfluoroalkyl substances (PFAS). Nonetheless, there is a scarcity of in vitro studies investigating the toxicity of MPs combined with these additives and deciphering the underlying mechanisms in the context of recurrent exposures, which more accurately reflect human contamination. The objective of this study is to assess the differential toxic impacts of polyethylene microplastics (PE-MPs, 100 μg/mL) and a mixture of additives (i.e., AddMix containing 10 μM of BPA, BPS, PFOS, and PFOA) on naive THP-1 macrophages during unique or three repeated exposures over five days. Scanning electron and Raman microscopy images indicated an effective internalization of PE-MPs by macrophages after 30 min and 24 h of exposure. Three repeated exposures of THP-1 macrophages to PE-MPs and PE-MPs + AddMix over five days increased mitochondrial ROS production by 19 % and 13 %, respectively, and led to a more pronounced glycolytic phenotype, associated with the enhanced secretion of the pro-inflammatory cytokine IL-1β by 38 % with PE-MPs. Analysis of transcriptomic data revealed that PE-MPs and/or AddMix significantly enhanced the expression of genes primarily related to inflammation and modulation of lipid metabolism pathways. Our work highlights that MPs mixtures with additives, particularly upon repeated exposure, are recognized by macrophages as activation signals, leading to stimulation of inflammatory pathways, which require further investigation to be fully deciphered.
SN  - 0269-7491
SN  - 1873-6424
ER  -