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The role of p53 in lung macrophages following exposure to a panel of manufactured nanomaterials

  • Nanotoxicology
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Abstract

Manufactured nanomaterials (MNMs) have the potential to improve everyday life as they can be utilised in numerous medical applications and day-to-day consumer products. However, this increased use has led to concerns about the potential environmental and human health impacts. The protein p53 is a key transcription factor implicated in cellular defence and reparative responses to various stress factors. Additionally, p53 has been implicated in cellular responses following exposure to some MNMs. Here, the role of the MNM mediated p53 induction and activation and its downstream effects following exposure to five well-characterised materials [namely two types of TiO2, two carbon black (CB), and one single-walled carbon nanotube (SWCNT)] were investigated. MNM internalisation, cellular viability, p53 protein induction and activation, oxidative stress, inflammation and apoptosis were measured in murine cell line and primary pulmonary macrophage models. It was observed that p53 was implicated in the biological responses to MNMs, with oxidative stress associated with p53 activation (only following exposure to the SWCNT). We demonstrate that p53 acted as an antioxidant and anti-inflammatory in macrophage responses to SWCNT and CB NMs. However, p53 was neither involved in MNM-induced cellular toxicity, nor in the apoptosis induced by these MNMs. Moreover, the physicochemical characteristics of MNMs seemed to influence their biological effects-SWCNT the materials with the largest surface area and a fibrous shape were the most cytotoxic in this study and were capable of the induction and activation of p53.

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Acknowledgments

This work was supported by the “Labex Serenade (11-LABX-0064)”, the “Agence nationale de sécurité sanitaire de l’Alimentation, de l’Environnement et du Travail”–PhD grants of Lucie Armand and Jean-Marie Gagliolo. Angélique Simon-Deckers was funded from ANR, while Sandra Chrusciel was supported by AREMCAR. Jorge Boczwoski and Sophie Lanone were both recipients of a Contrat de Recherche Translationnelle, between Inserm and CHU Mondor (JB) and Inserm and CHI Créteil (SL). Finally, a special thank you to the Hospital University Department (DHU) Aging-Thorax, Vessels, Blood (A-TVB) for their support of this study.

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. University Paris est Val de Marne (UPEC), Créteil, 94000, France

    Esther Belade, Sandra Chrusciel, Lucie Armand, Angélique Simon-Deckers, Philippe Caramelle, Jean-Marie Gagliolo, Laurent Boyer, Sophie Lanone, Jean-Claude Pairon, Ali Kermanizadeh & Jorge Boczkowski

  2. INSERM U955, Equipe 04, Faculté de Médecine de Créteil, 8 rue du Général Sarrail, 94000, Créteil, France

    Esther Belade, Sandra Chrusciel, Lucie Armand, Angélique Simon-Deckers, Philippe Caramelle, Jean-Marie Gagliolo, Laurent Boyer, Sophie Lanone, Jean-Claude Pairon, Ali Kermanizadeh & Jorge Boczkowski

  3. Nanomedicine Laboratory, Faculty of Medical and Human Sciences, Institute of Inflammation and Repair, and National Graphene Institute, University of Manchester, Manchester, M13 9PT, UK

    Cyrill Bussy

  4. Hôpital Intercommunal de Créteil, Service de Pneumologie et Pathologie Professionnelle, Créteil, 94000, France

    Jean-Claude Pairon & Jorge Boczkowski

  5. Department of Public Health, Section of Environmental Health, University of Copenhagen, 1014, Copenhagen, Denmark

    Ali Kermanizadeh

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  1. Esther Belade
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  2. Sandra Chrusciel
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Correspondence to Ali Kermanizadeh or Jorge Boczkowski.

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Belade, E., Chrusciel, S., Armand, L. et al. The role of p53 in lung macrophages following exposure to a panel of manufactured nanomaterials. Arch Toxicol 89, 1543–1556 (2015). https://doi.org/10.1007/s00204-014-1324-5

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