Publication: MOLECULAR MECHANISMS OF TOXICITY INDUCED BY POLYFLUOROALKYL SUBSTANCES IN HUMAN BRONCHIAL EPITHELIAL CELLS AND LUNG FIBROBLASTS
| dc.contributor.author | CINDY YEOH SHIN LY | |
| dc.date.accessioned | 2025-07-14T02:29:21Z | |
| dc.date.available | 2025-07-14T02:29:21Z | |
| dc.date.issued | 2024 | |
| dc.description.abstract | Per- and polyfluoroalkyl substances (PFASs) are extensively utilised in various industrial and commercial application due to their exceptional thermal stability, low surface tension, and water- and oil-repellent properties, such as the production of nonstick coatings ion cookware, bakeware, disposable food packaging, stain- and water-resistant textiles. Among these, perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are the most extensively studied and well-known PFAS. Their bioaccumulation and persistence pose adverse effects on human health, primarily lungs, liver and kidneys. Despite their known effects, the specific mechanisms underlying PFAS-induced respiratory toxicity remained poorly understood. This study investigated the molecular mechanisms of lung toxicity induced by PFOA and PFOS in human normal bronchial epithelial BEAS-2B cells and normal lung MRC-5 fibroblasts. Our findings demonstrated that both PFOA and PFOS induced apoptosis and altered cell cycle distribution pattern in human lung cells. KEGG pathway analysis identified IL-17 and TNF signalling pathways as the potential modulated toxicity pathways responsible for PFOA and PFOS-induced apoptosis and altered cell cycle distribution pattern. Further analysis revealed significant upregulation of transcription factors (FOSL1 and CREB5) and proinflammatory cytokines (IL-6 and CXCL8), in response to PFOA or PFOS exposure. Functional validation studies demonstrated that 666-15 (selective CREB inhibitor) effectively ameliorated the overexpression of IL-6 and CXCL8 induced by PFOA and PFOS. While T-5224 (selective FOSL1 inhibitor) only ameliorated the overexpression of IL-6 and CXCL8 by PFOA, but not PFOS. Taken together, PFOA or PFOS may play a potential role in mediating the release of pro-inflammatory cytokines and lung inflammation, primarily through TNF and IL-17 signalling pathways, with potential involvement of other pathways such as NF-κB signalling pathway. | |
| dc.identifier.uri | https://hdl.handle.net/20.500.14377/37110 | |
| dc.language.iso | en | |
| dc.publisher | IMU University | |
| dc.subject | Gene Expression Regulation | |
| dc.subject | Fluorocarbons | |
| dc.subject | Epithelial Cells | |
| dc.subject | Fibroblasts | |
| dc.subject | Apoptosis | |
| dc.title | MOLECULAR MECHANISMS OF TOXICITY INDUCED BY POLYFLUOROALKYL SUBSTANCES IN HUMAN BRONCHIAL EPITHELIAL CELLS AND LUNG FIBROBLASTS | |
| dc.type | Thesis | |
| dspace.entity.type | Publication | |
| oairecerif.author.affiliation | #PLACEHOLDER_PARENT_METADATA_VALUE# |