HIF-1 alpha is a key mediator of the lung inflammatory potential of lithium-ion battery particles
Sironval, V; Palmai-Pallag, M; Vanbever, R; Huaux, F; Mejia, J; Lucas, S; Lison, D; van Den Brule, S; ,
| HERO ID | 6792655 |
|---|---|
| In Press | No |
| Year | 2019 |
| Title | HIF-1 alpha is a key mediator of the lung inflammatory potential of lithium-ion battery particles |
| Authors | Sironval, V; Palmai-Pallag, M; Vanbever, R; Huaux, F; Mejia, J; Lucas, S; Lison, D; van Den Brule, S; , |
| Journal | Particle and Fibre Toxicology |
| Volume | 16 |
| Issue | 1 |
| Page Numbers | 35 |
| 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) -1 alpha, a factor implicated in inflammation, fibrosis and carcinogenicity. Here, we investigated the role of cobalt, nickel and HIF-1 alpha 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-1 alpha in the lung. Inhibition of HIF-1 alpha with chetomin or PX-478 blunted the lung inflammatory response to LCO in mice. In IL-1 beta deficient mice, HIF-1 alpha was the upstream signal of the inflammatory lung response to LCO. In vitro, the level of HIF-1 alpha 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-1 alpha, 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-1 alpha in vitro can be used to predict the lung inflammatory potential of LIB particles. |
| Doi | 10.1186/s12989-019-0319-z |
| Pmid | 31533843 |
| Wosid | WOS:000491229500001 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |