Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA.
Department of Environmental Health, School of Public Health, Boston University, Boston, MA 02118, USA.
Int J Mol Sci. 2023 May 10;24(10):8539. doi: 10.3390/ijms24108539.
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.
已知接触全氟和多氟烷基物质（PFAS）会对肺部造成不良影响，但作用机制尚不清楚。为了探索这一点，我们培养了人支气管上皮细胞，并将其暴露于不同浓度的短链（全氟丁烷酸、全氟丁烷磺酸和 GenX）或长链（PFOA 和全氟辛烷磺酸（PFOS））PFAS 中，单独或混合，以确定细胞毒性浓度。从该实验中选择非细胞毒性浓度的 PFAS，以评估 NLRP3 炎性体的激活和启动。我们发现，与载体对照相比，PFOA 和 PFOS 单独或混合可启动和激活炎性体。原子力显微镜显示，PFOA 但不是 PFOS 会显著改变细胞的膜性质。对饮用水中摄入 PFOA 14 周的小鼠的肺部进行了 RNA 测序。WT、PPARα 敲除（KO）和人源化 PPARα（KI）接受了 PFOA 的暴露。我们发现，多个炎症和免疫相关基因受到影响。总之，我们的研究表明，PFAS 暴露可能以显著的方式改变肺部生物学，并可能导致哮喘/气道高反应性。
