title: The role of p53 in lung macrophages following exposure to a panel of manufactured nanomaterials.
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.
authors.affiliation: University Paris est Val de Marne (UPEC), Créteil, 94000, France.
authors.forename: Esther
authors.initials: E
authors.lastname: Belade
authors.forename: Sandra
authors.initials: S
authors.lastname: Chrusciel
authors.forename: Lucie
authors.initials: L
authors.lastname: Armand
authors.forename: Angélique
authors.initials: A
authors.lastname: Simon-Deckers
authors.forename: Cyrill
authors.initials: C
authors.lastname: Bussy
authors.forename: Philippe
authors.initials: P
authors.lastname: Caramelle
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Gagliolo
authors.forename: Laurent
authors.initials: L
authors.lastname: Boyer
authors.forename: Sophie
authors.initials: S
authors.lastname: Lanone
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Pairon
authors.forename: Ali
authors.initials: A
authors.lastname: Kermanizadeh
authors.forename: Jorge
authors.initials: J
authors.lastname: Boczkowski
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival; D007249:Inflammation / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D049329:Nanostructures / Q000633:toxicity*; D037742:Nanotubes, Carbon / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D014025:Titanium / Q000008:administration & dosage / Q000633:toxicity; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D037742:Nanotubes, Carbon; D016159:Tumor Suppressor Protein p53; C009495:titanium dioxide; D014025:Titanium