HIF-1? 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 inflammatory and fibrotic lung responses in mice. LCO also stabilizes hypoxia-inducible factor (HIF) -1?, a factor implicated in inflammation, fibrosis and carcinogenicity. Here, we investigated the role of cobalt, nickel and HIF-1? 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? in the lung. Inhibition of HIF-1? with chetomin or PX-478 blunted the lung inflammatory response to LCO in mice. In IL-1? deficient mice, HIF-1? was the upstream signal of the inflammatory lung response to LCO. In vitro, the level of HIF-1? 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?, 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? in vitro can be used to predict the lung inflammatory potential of LIB particles.

SUBMITTER: Sironval V 

PROVIDER: S-EPMC6751682 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature