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| Natura: | Artículo científico |
| Lingua: | en |
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Toxicology
2025
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| Accesso online: | https://pubmed.ncbi.nlm.nih.gov/40199452/ |
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| author | Kim, Da Hye Lee, Hyesook Kim, Min Yeong Hwangbo, Hyun Ji, Seon Yeong Bang, EunJin Hong, Su Hyun Kim, Gi Young Leem, Sun-Hee Ryu, Dongryeol Cheong, JaeHun Choi, Yung Hyun |
| author_facet | Kim, Da Hye Lee, Hyesook Kim, Min Yeong Hwangbo, Hyun Ji, Seon Yeong Bang, EunJin Hong, Su Hyun Kim, Gi Young Leem, Sun-Hee Ryu, Dongryeol Cheong, JaeHun Choi, Yung Hyun Kim, Da Hye Lee, Hyesook Kim, Min Yeong Hwangbo, Hyun Ji, Seon Yeong Bang, EunJin Hong, Su Hyun Kim, Gi Young Leem, Sun-Hee Ryu, Dongryeol Cheong, JaeHun Choi, Yung Hyun |
| collection | PubMed - marine biology |
| contents | Particulate matter 2.5 stimulates pyroptosis and necroptosis via the p38 MAPK/Akt/NF-κB signaling pathway in human corneal epithelial cells. Kim, Da Hye Lee, Hyesook Kim, Min Yeong Hwangbo, Hyun Ji, Seon Yeong Bang, EunJin Hong, Su Hyun Kim, Gi Young Leem, Sun-Hee Ryu, Dongryeol Cheong, JaeHun Choi, Yung Hyun Humans Particulate Matter Pyroptosis Necroptosis NF-kappa B Proto-Oncogene Proteins c-akt p38 Mitogen-Activated Protein Kinases Signal Transduction Reactive Oxygen Species NLR Family, Pyrin Domain-Containing 3 Protein Epithelium, Corneal Epithelial Cells Cell Survival Cell Line Inflammasomes Dose-Response Relationship, Drug Particulate matter 2.5 (PM) exposure poses significant health risks, particularly to the eyes. This study aimed to investigate the cytotoxic effects of PM on human corneal epithelial cells (HCECs) and to elucidate the mechanisms involved in pyroptosis and necroptosis. HCECs were exposed to PM, and cytotoxicity, reactive oxygen species (ROS) levels, and the expression of pyroptosis- and necroptosis-related proteins were assessed. The roles of nuclear factor-kappa B (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signaling pathways were also investigated. Exposure to PM caused a dose-dependent decrease in cell viability, accompanied by significant NLRP3 inflammasome activation, leading to pyroptosis and the release of pro-inflammatory cytokines. Enhanced ROS generation and mitochondrial dysfunction have also been observed, along with indicators of necroptosis, such as increased levels of mixed-lineage kinase domain-like proteins. Importantly, activation of the NF-κB signaling pathway was crucial for these responses. The suppression of p38 mitogen-activated protein kinase (MAPK) and activation of protein kinase B (Akt) using pharmacological modulators SB203580 and SC79, respectively, significantly reduced PM-mediated cellular damage. These findings indicate that p38 MAPK inhibition and Akt activation are key regulatory mechanisms that help attenuate the deleterious effects of PM on HCECs. In conclusion, our findings offer new insights into the mechanisms by which PM induces pyroptosis and necroptosis in HCECs, especially by activating the NLRP3 inflammasome and NF-κB signaling pathways. The critical regulatory roles of p38 MAPK and Akt underscore their potential as therapeutic targets to alleviate PM-induced ocular damage. |
| format | Artículo científico |
| id | pubmed_40199452 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Toxicology |
| record_format | pubmed |
| spellingShingle | Particulate matter 2.5 stimulates pyroptosis and necroptosis via the p38 MAPK/Akt/NF-κB signaling pathway in human corneal epithelial cells. Kim, Da Hye Lee, Hyesook Kim, Min Yeong Hwangbo, Hyun Ji, Seon Yeong Bang, EunJin Hong, Su Hyun Kim, Gi Young Leem, Sun-Hee Ryu, Dongryeol Cheong, JaeHun Choi, Yung Hyun Humans Particulate Matter Pyroptosis Necroptosis NF-kappa B Proto-Oncogene Proteins c-akt p38 Mitogen-Activated Protein Kinases Signal Transduction Reactive Oxygen Species NLR Family, Pyrin Domain-Containing 3 Protein Epithelium, Corneal Epithelial Cells Cell Survival Cell Line Inflammasomes Dose-Response Relationship, Drug Particulate matter 2.5 stimulates pyroptosis and necroptosis via the p38 MAPK/Akt/NF-κB signaling pathway in human corneal epithelial cells. Kim, Da Hye Lee, Hyesook Kim, Min Yeong Hwangbo, Hyun Ji, Seon Yeong Bang, EunJin Hong, Su Hyun Kim, Gi Young Leem, Sun-Hee Ryu, Dongryeol Cheong, JaeHun Choi, Yung Hyun Humans Particulate Matter Pyroptosis Necroptosis NF-kappa B Proto-Oncogene Proteins c-akt p38 Mitogen-Activated Protein Kinases Signal Transduction Reactive Oxygen Species NLR Family, Pyrin Domain-Containing 3 Protein Epithelium, Corneal Epithelial Cells Cell Survival Cell Line Inflammasomes Dose-Response Relationship, Drug Particulate matter 2.5 (PM) exposure poses significant health risks, particularly to the eyes. This study aimed to investigate the cytotoxic effects of PM on human corneal epithelial cells (HCECs) and to elucidate the mechanisms involved in pyroptosis and necroptosis. HCECs were exposed to PM, and cytotoxicity, reactive oxygen species (ROS) levels, and the expression of pyroptosis- and necroptosis-related proteins were assessed. The roles of nuclear factor-kappa B (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signaling pathways were also investigated. Exposure to PM caused a dose-dependent decrease in cell viability, accompanied by significant NLRP3 inflammasome activation, leading to pyroptosis and the release of pro-inflammatory cytokines. Enhanced ROS generation and mitochondrial dysfunction have also been observed, along with indicators of necroptosis, such as increased levels of mixed-lineage kinase domain-like proteins. Importantly, activation of the NF-κB signaling pathway was crucial for these responses. The suppression of p38 mitogen-activated protein kinase (MAPK) and activation of protein kinase B (Akt) using pharmacological modulators SB203580 and SC79, respectively, significantly reduced PM-mediated cellular damage. These findings indicate that p38 MAPK inhibition and Akt activation are key regulatory mechanisms that help attenuate the deleterious effects of PM on HCECs. In conclusion, our findings offer new insights into the mechanisms by which PM induces pyroptosis and necroptosis in HCECs, especially by activating the NLRP3 inflammasome and NF-κB signaling pathways. The critical regulatory roles of p38 MAPK and Akt underscore their potential as therapeutic targets to alleviate PM-induced ocular damage. |
| title | Particulate matter 2.5 stimulates pyroptosis and necroptosis via the p38 MAPK/Akt/NF-κB signaling pathway in human corneal epithelial cells. |
| topic | Humans Particulate Matter Pyroptosis Necroptosis NF-kappa B Proto-Oncogene Proteins c-akt p38 Mitogen-Activated Protein Kinases Signal Transduction Reactive Oxygen Species NLR Family, Pyrin Domain-Containing 3 Protein Epithelium, Corneal Epithelial Cells Cell Survival Cell Line Inflammasomes Dose-Response Relationship, Drug |
| url | https://pubmed.ncbi.nlm.nih.gov/40199452/ |