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Exposure to multi-walled carbon nanotubes results in aggravation of airway inflammation and remodeling and in increased production of epithelium-derived innate cytokines in a mouse model of asthma

  • Organ Toxicity and Mechanisms
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Abstract

With the development of nanotechnologies, the potential adverse effects of nanomaterials such as multi-walled carbon nanotubes (MWCNT) on the respiratory tract of asthmatics are questioned. Furthermore, investigations are necessary to understand how these effects might arise. In the present study, we hypothesized that epithelium-derived innate cytokines that are considered as important promoting factors in allergy may contribute to an aggravating effect of MWCNT on asthma. We investigated in the mouse the effect of MWCNT on systemic immune response and airway inflammation and remodeling induced by the most frequent allergen so far associated with asthma, house dust mite (HDM), and we examined the production of the innate cytokines thymic stromal lymphopoietin (TSLP), IL-25, IL-33, and GM-CSF. Mice exposed to HDM exhibited specific IgG1 in serum and inflammatory cell infiltration, and increased Th2 cytokine production, mucus hyperproduction, and collagen deposition in the airways when compared to naïve animals. Levels of total IgG1 and HDM-specific IgG1, influx of macrophages, eosinophils and neutrophils, production of collagen, TGF-β1, and mucus, as well as levels of IL-13, eotaxin, and TARC, were dose-dependently increased in mice exposed to HDM and MWCNT compared to HDM alone. These effects were associated with an increased production of TSLP, IL-25, IL-33, and GM-CSF in the airways. Our data demonstrate that MWCNT increase in a dose-dependent manner systemic immune response, as well as airway allergic inflammation and remodeling induced by HDM in the mouse. Our data suggest also a role for airway epithelium and innate cytokines in these effects.

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Acknowledgments

This work was supported by the Agence Nationale de la Recherche (ANR-08-CESA-017), the Centre National de la Recherche Scientifique, the Université de Strasbourg, and the Réseau Alsace de Laboratoires en Ingénierie et Sciences pour l’Environnement. Carole Ronzani is the recipient of a PhD grant from the Ministère de l’Education Nationale, de la Recherche et de la Technologie. The authors thank the laboratory of the Unité de Pneumologie, d’Allergologie et de Pathologie respiratoire de l’environnement at the Hôpitaux Universitaires de Strasbourg, for endotoxin assays.

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  1. Faculté de Pharmacie, Laboratoire de Conception et Application de Molécules Bioactives, CNRS, Université de Strasbourg, 74 route du Rhin, BP 60024, 67401, Illkirch Cedex, France

    Carole Ronzani, Anne Casset & Françoise Pons

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  1. Carole Ronzani
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Ronzani, C., Casset, A. & Pons, F. Exposure to multi-walled carbon nanotubes results in aggravation of airway inflammation and remodeling and in increased production of epithelium-derived innate cytokines in a mouse model of asthma. Arch Toxicol 88, 489–499 (2014). https://doi.org/10.1007/s00204-013-1116-3

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