Perfluoroalkyl Substances (PFAS) Affect Inflammation in Lung Cells and Tissues

Adverse lung outcomes from exposure to per-and polyfluoroalkyl substances (PFAS) are known; however, the mechanism of action is poorly understood. To explore this, human bronchial epithelial cells were grown and exposed to varied concentrations of short-chain (perfluorobutanoic acid, perflurobutane...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-05, Vol.24 (10), p.8539
Main Authors: Dragon, Julie, Hoaglund, Michael, Badireddy, Appala Raju, Nielsen, Greylin, Schlezinger, Jennifer, Shukla, Arti
Format: Article
Language:English
Subjects:
Alkanesulfonic Acids - toxicity
Ammonium perfluorooctanoate
Animals
Apoptosis
Asthma
Atomic force microscopy
Comparative analysis
Cytokines
Cytotoxicity
Drinking water
Environmental Pollutants
Epithelial cells
Epithelium
Exposure
Fluorocarbons - toxicity
Gene expression
Humans
inflammasome
Inflammasomes
Inflammation
lung
Lung - chemistry
Lungs
Mice
Mixtures
Pathogenesis
Perfluoro compounds
Perfluoroalkyl & polyfluoroalkyl substances
Perfluorooctane sulfonic acid
Perfluorooctanoic acid
PFAS
PPAR alpha
Proteins
RNA
RNA sequencing
Sulfonic acid
Surfactants
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Summary:Adverse lung outcomes from exposure to per-and polyfluoroalkyl substances (PFAS) are known; however, the mechanism of action is poorly understood. To explore this, human bronchial epithelial cells were grown and exposed to varied concentrations of short-chain (perfluorobutanoic acid, perflurobutane sulfonic acid and GenX) or long-chain (PFOA and perfluorooctane sulfonic acid (PFOS)) PFAS, alone or in a mixture to identify cytotoxic concentrations. Non-cytotoxic concentrations of PFAS from this experiment were selected to assess NLRP3 inflammasome activation and priming. We found that PFOA and PFOS alone or in a mixture primed and activated the inflammasome compared with vehicle control. Atomic force microscopy showed that PFOA but not PFOS significantly altered the membrane properties of cells. RNA sequencing was performed on the lungs of mice that had consumed PFOA in drinking water for 14 weeks. Wild type (WT), PPARα knock-out (KO) and humanized PPARα (KI) were exposed to PFOA. We found that multiple inflammation- and immune-related genes were affected. Taken together, our study demonstrated that PFAS exposure could alter lung biology in a significant manner and may contribute to asthma/airway hyper-responsiveness.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms24108539