TY - JOUR

T1 - The role of p53 in lung macrophages following exposure to a panel of manufactured nanomaterials

AU - Belade, Esther

AU - Chrusciel, Sandra

AU - Armand, Lucie

AU - Simon-Deckers, Angélique

AU - Bussy, Cyrill

AU - Caramelle, Philippe

AU - Gagliolo, Jean-Marie

AU - Boyer, Laurent

AU - Lanone, Sophie

AU - Pairon, Jean-Claude

AU - Kermanizadeh, Ali

AU - Boczkowski, Jorge

PY - 2015/9

Y1 - 2015/9

N2 - 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.

AB - 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.

KW - Animals

KW - Apoptosis/drug effects

KW - Cell Line

KW - Cell Survival

KW - Inflammation/pathology

KW - Macrophages, Alveolar/drug effects

KW - Mice

KW - Mice, Knockout

KW - Nanostructures/toxicity

KW - Nanotubes, Carbon/toxicity

KW - Oxidative Stress/drug effects

KW - Titanium/administration & dosage

KW - Tumor Suppressor Protein p53/genetics

U2 - 10.1007/s00204-014-1324-5

DO - 10.1007/s00204-014-1324-5

M3 - Article

C2 - 25098341

VL - 89

SP - 1543

EP - 1556

JO - Archives of toxicology

JF - Archives of toxicology

SN - 0340-5761

IS - 9

ER -