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

Area of Science:

• Environmental Health
• Toxicology
• Cell Biology

Background:

• Adverse lung outcomes linked to per- and polyfluoroalkyl substances (PFAS) are recognized, but underlying mechanisms remain unclear.
• Understanding how PFAS affect lung cells and inflammatory pathways is crucial for assessing health risks.

Purpose of the Study:

• To investigate the cellular mechanisms by which short-chain and long-chain PFAS impact human bronchial epithelial cells.
• To examine the activation of the NLRP3 inflammasome and alterations in cell membrane properties following PFAS exposure.
• To analyze the effects of perfluorooctanoic acid (PFOA) on lung gene expression in mice with varying PPARα activity.

Main Methods:

• Human bronchial epithelial cells were exposed to various concentrations of short-chain (e.g., GenX) and long-chain (e.g., PFOA, PFOS) PFAS to determine cytotoxic levels.
• Non-cytotoxic PFAS concentrations were used to assess NLRP3 inflammasome priming and activation.
• Atomic force microscopy evaluated changes in cell membrane properties.
• RNA sequencing analyzed gene expression in mouse lungs after chronic PFOA exposure.

Main Results:

• PFOA and perfluorooctane sulfonic acid (PFOS) primed and activated the NLRP3 inflammasome in lung cells.
• PFOA significantly altered cell membrane properties, while PFOS did not.
• PFOA exposure in mice led to significant changes in inflammation- and immune-related genes, particularly in wild-type and PPARα variants.

Conclusions:

• PFAS exposure can significantly alter lung biology, including inflammasome activation and gene expression.
• Observed changes suggest a potential role for PFAS in the development of asthma and airway hyper-responsiveness.
• Further research into PFAS toxicology and mechanisms of lung injury is warranted.