HIF-1α is a key mediator of the lung inflammatory potential of lithium-ion battery particles
Abstract Background Li-ion batteries (LIB) are increasingly used worldwide. They are made of low solubility micrometric particles, implying a potential for inhalation toxicity in occupational settings and possibly for consumers. LiCoO2 (LCO), one of the most used cathode material, induces inflammato...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-09-01
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| Series: | Particle and Fibre Toxicology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12989-019-0319-z |
| _version_ | 1831741193738780672 |
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| author | Violaine Sironval Mihaly Palmai-Pallag Rita Vanbever François Huaux Jorge Mejia Stéphane Lucas Dominique Lison Sybille van den Brule |
| author_facet | Violaine Sironval Mihaly Palmai-Pallag Rita Vanbever François Huaux Jorge Mejia Stéphane Lucas Dominique Lison Sybille van den Brule |
| author_sort | Violaine Sironval |
| collection | DOAJ |
| description | Abstract Background Li-ion batteries (LIB) are increasingly used worldwide. They are made of low solubility micrometric particles, implying a potential for inhalation toxicity in occupational settings and possibly for consumers. LiCoO2 (LCO), one of the most used cathode material, induces inflammatory and fibrotic lung responses in mice. LCO also stabilizes hypoxia-inducible factor (HIF) -1α, a factor implicated in inflammation, fibrosis and carcinogenicity. Here, we investigated the role of cobalt, nickel and HIF-1α as determinants of toxicity, and evaluated their predictive value for the lung toxicity of LIB particles in in vitro assays. Results By testing a set of 5 selected LIB particles (LCO, LiNiMnCoO2, LiNiCoAlO2) with different cobalt and nickel contents, we found a positive correlation between their in vivo lung inflammatory activity, and (i) Co and Ni particle content and their bioaccessibility and (ii) the stabilization of HIF-1α in the lung. Inhibition of HIF-1α with chetomin or PX-478 blunted the lung inflammatory response to LCO in mice. In IL-1β deficient mice, HIF-1α was the upstream signal of the inflammatory lung response to LCO. In vitro, the level of HIF-1α stabilization induced by LIB particles in BEAS-2B cells correlated with the intensity of lung inflammation induced by the same particles in vivo. Conclusions We conclude that HIF-1α, stabilized in lung cells by released Co and Ni ions, is a mechanism-based biomarker of lung inflammatory responses induced by LIB particles containing Co/Ni. Documenting the Co/Ni content of LIB particles, their bioaccessibility and their capacity to stabilize HIF-1α in vitro can be used to predict the lung inflammatory potential of LIB particles. |
| first_indexed | 2024-12-21T14:12:14Z |
| format | Article |
| id | doaj.art-11e3a7e0359e46ae9f89399e1a1cafa4 |
| institution | Directory Open Access Journal |
| issn | 1743-8977 |
| language | English |
| last_indexed | 2024-12-21T14:12:14Z |
| publishDate | 2019-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Particle and Fibre Toxicology |
| spelling | doaj.art-11e3a7e0359e46ae9f89399e1a1cafa42022-12-21T19:01:00ZengBMCParticle and Fibre Toxicology1743-89772019-09-0116111210.1186/s12989-019-0319-zHIF-1α is a key mediator of the lung inflammatory potential of lithium-ion battery particlesViolaine Sironval0Mihaly Palmai-Pallag1Rita Vanbever2François Huaux3Jorge Mejia4Stéphane Lucas5Dominique Lison6Sybille van den Brule7Louvain centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de LouvainLouvain centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de LouvainLouvain Drug Research Institute, Université catholique de LouvainLouvain centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de LouvainResearch Centre for the Physics of Matter and Radiation (PMR-LARN), NARILIS, Université de NamurResearch Centre for the Physics of Matter and Radiation (PMR-LARN), NARILIS, Université de NamurLouvain centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de LouvainLouvain centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de LouvainAbstract Background Li-ion batteries (LIB) are increasingly used worldwide. They are made of low solubility micrometric particles, implying a potential for inhalation toxicity in occupational settings and possibly for consumers. LiCoO2 (LCO), one of the most used cathode material, induces inflammatory and fibrotic lung responses in mice. LCO also stabilizes hypoxia-inducible factor (HIF) -1α, a factor implicated in inflammation, fibrosis and carcinogenicity. Here, we investigated the role of cobalt, nickel and HIF-1α as determinants of toxicity, and evaluated their predictive value for the lung toxicity of LIB particles in in vitro assays. Results By testing a set of 5 selected LIB particles (LCO, LiNiMnCoO2, LiNiCoAlO2) with different cobalt and nickel contents, we found a positive correlation between their in vivo lung inflammatory activity, and (i) Co and Ni particle content and their bioaccessibility and (ii) the stabilization of HIF-1α in the lung. Inhibition of HIF-1α with chetomin or PX-478 blunted the lung inflammatory response to LCO in mice. In IL-1β deficient mice, HIF-1α was the upstream signal of the inflammatory lung response to LCO. In vitro, the level of HIF-1α stabilization induced by LIB particles in BEAS-2B cells correlated with the intensity of lung inflammation induced by the same particles in vivo. Conclusions We conclude that HIF-1α, stabilized in lung cells by released Co and Ni ions, is a mechanism-based biomarker of lung inflammatory responses induced by LIB particles containing Co/Ni. Documenting the Co/Ni content of LIB particles, their bioaccessibility and their capacity to stabilize HIF-1α in vitro can be used to predict the lung inflammatory potential of LIB particles.http://link.springer.com/article/10.1186/s12989-019-0319-zPredictive toxicologyIL-1β, Epithelial cellsBiomarkerCobaltNickel |
| spellingShingle | Violaine Sironval Mihaly Palmai-Pallag Rita Vanbever François Huaux Jorge Mejia Stéphane Lucas Dominique Lison Sybille van den Brule HIF-1α is a key mediator of the lung inflammatory potential of lithium-ion battery particles Particle and Fibre Toxicology Predictive toxicology IL-1β, Epithelial cells Biomarker Cobalt Nickel |
| title | HIF-1α is a key mediator of the lung inflammatory potential of lithium-ion battery particles |
| title_full | HIF-1α is a key mediator of the lung inflammatory potential of lithium-ion battery particles |
| title_fullStr | HIF-1α is a key mediator of the lung inflammatory potential of lithium-ion battery particles |
| title_full_unstemmed | HIF-1α is a key mediator of the lung inflammatory potential of lithium-ion battery particles |
| title_short | HIF-1α is a key mediator of the lung inflammatory potential of lithium-ion battery particles |
| title_sort | hif 1α is a key mediator of the lung inflammatory potential of lithium ion battery particles |
| topic | Predictive toxicology IL-1β, Epithelial cells Biomarker Cobalt Nickel |
| url | http://link.springer.com/article/10.1186/s12989-019-0319-z |
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