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.

Therapeutic efficacy of the novel selective RNA polymerase I inhibitor CX‐5461 on pulmonary arterial hypertension and associated vascular remodelling

“…Further analysis of the specific effects of Pol I inhibition in these macrophage subpopulations is needed. Indeed, there is evidence suggesting that p53 has an anti-inflammatory role in macrophages (Belade et al, 2015;Mukhopadhyay et al, 2017;Zheng et al, 2005), which supports our findings of the antiinflammatory effects of CX-5461.…”

Shape-Related Toxicity of Titanium Dioxide Nanofibres

“…However, this modest intrinsic reactivity did not result in a marked cell oxidative damage, as demonstrated by the lack of lipid peroxidation, although at least two distinct parameters clearly indicate the occurrence of oxidative stress in NF-treated cells were a) a limited reduction in the cellular GSH and b) a slight induction of Hmox1 , one of the most sensitive and reliable indicators of the cell response to oxidative stress, which is linked to inflammation triggering [ 31 ]. In agreement with observations of others [ 58 ], oxidative stress also occurs in Raw 264.7 macrophages exposed to TiO 2 NP, as demonstrated by GSH decrease and Hmox1 induction. Given that both effective and frustrated phagocytosis lead to the generation of superoxide free radicals (O 2 •- ) [ 52 , 59 ], it is likely that in macrophages exposed to either NF or NP, a limited oxidative stress ensues that triggers NF-κB-dependent induction of pro-inflammatory genes.…”

Molecular responses of alveolar epithelial A549 cells to chronic exposure to titanium dioxide nanoparticles: A proteomic view

“…By increasing STRAP intracellular content, chronic exposure to TiO 2 -NPs thus induces DNA damage response, which may lead to the transcription of DNA repair genes. Finally phosphorylation of p53 [52] cell proliferation impairment [53] and activation of the ATM…”