HIF-1α is a key mediator of the lung inflammatory potential of lithium-ion battery particles

Violaine Sironval, Mihaly Palmai-Pallag, Rita Vanbever, François Huaux, Jorge Humberto Mejia Mendoza, Stéphane Lucas, Dominique Lison, Sybille van den Brule

Résultats de recherche: Contribution à un journal/une revueArticle

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Résumé

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.
langue originaleAnglais
Nombre de pages12
journalParticle and Fibre Toxicology
Volume16
Numéro de publication35
Les DOIs
étatPublié - 18 sept. 2019

Empreinte digitale

Hypoxia-Inducible Factor 1
Lithium
Ions
Lung
Cobalt
Nickel
Interleukin-1
Solubility
Inhalation
Pneumonia
Electrodes
Fibrosis
Biomarkers
Inflammation

Citer ceci

Sironval, Violaine ; Palmai-Pallag, Mihaly ; Vanbever, Rita ; Huaux, François ; Mejia Mendoza, Jorge Humberto ; Lucas, Stéphane ; Lison, Dominique ; van den Brule, Sybille . / HIF-1α is a key mediator of the lung inflammatory potential of lithium-ion battery particles. Dans: Particle and Fibre Toxicology. 2019 ; Vol 16, Numéro 35.
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title = "HIF-1α is a key mediator of the lung inflammatory potential of lithium-ion battery particles",
abstract = "BackgroundLi-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.ResultsBy 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.ConclusionsWe 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.",
author = "Violaine Sironval and Mihaly Palmai-Pallag and Rita Vanbever and Fran{\cc}ois Huaux and {Mejia Mendoza}, {Jorge Humberto} and St{\'e}phane Lucas and Dominique Lison and {van den Brule}, Sybille",
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HIF-1α is a key mediator of the lung inflammatory potential of lithium-ion battery particles. / Sironval, Violaine ; Palmai-Pallag, Mihaly ; Vanbever, Rita ; Huaux, François ; Mejia Mendoza, Jorge Humberto; Lucas, Stéphane; Lison, Dominique; van den Brule, Sybille .

Dans: Particle and Fibre Toxicology, Vol 16, Numéro 35, 18.09.2019.

Résultats de recherche: Contribution à un journal/une revueArticle

TY - JOUR

T1 - HIF-1α is a key mediator of the lung inflammatory potential of lithium-ion battery particles

AU - Sironval, Violaine

AU - Palmai-Pallag, Mihaly

AU - Vanbever, Rita

AU - Huaux, François

AU - Mejia Mendoza, Jorge Humberto

AU - Lucas, Stéphane

AU - Lison, Dominique

AU - van den Brule, Sybille

PY - 2019/9/18

Y1 - 2019/9/18

N2 - BackgroundLi-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.ResultsBy 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.ConclusionsWe 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.

AB - BackgroundLi-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.ResultsBy 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.ConclusionsWe 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.

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DO - https://particleandfibretoxicology.biomedcentral.com/articles/10.1186/s12989-019-0319-z

M3 - Article

VL - 16

JO - Particle and Fibre Toxicology

JF - Particle and Fibre Toxicology

SN - 1743-8977

IS - 35

ER -