Profiling of Sub-Lethal in Vitro Effects of Multi-Walled Carbon Nanotubes Reveals Changes in Chemokines and Chemokine Receptors.

Sandeep Keshavan,Wei Chen,Fernando Torres Andón,Bengt Fadeel,Audrey Gallud,Lang Tran,Knut Reinert

doi:10.3390/nano11040883

Abstract

Engineered nanomaterials are potentially very useful for a variety of applications, but studies are needed to ascertain whether these materials pose a risk to human health. Here, we studied three benchmark nanomaterials (Ag nanoparticles, TiO2 nanoparticles, and multi-walled carbon nanotubes, MWCNTs) procured from the nanomaterial repository at the Joint Research Centre of the European Commission. Having established a sub-lethal concentration of these materials using two human cell lines representative of the immune system and the lungs, respectively, we performed RNA sequencing of the macrophage-like cell line after exposure for 6, 12, and 24 h. Downstream analysis of the transcriptomics data revealed significant effects on chemokine signaling pathways. CCR2 was identified as the most significantly upregulated gene in MWCNT-exposed cells. Using multiplex assays to evaluate cytokine and chemokine secretion, we could show significant effects of MWCNTs on several chemokines, including CCL2, a ligand of CCR2. The results demonstrate the importance of evaluating sub-lethal concentrations of nanomaterials in relevant target cells.

Highlights

Nanotoxicology is a scientific discipline aimed at assessing the potential adverse effects of engineered nanomaterials (NMs) as well as enabling the safe use of NMs [1].Nanotoxicology research has made great strides in the past ten to fifteen years, and efforts to pin down the mechanism(s) of NM toxicity may inform regulatory frameworks with the goal of exploiting nanotechnology in a safe and sustainable manner [2]
The test materials [Ag (NM300K), TiO2 (NM104), and multi-walled carbon nanotubes (MWCNTs) (NM401)] were obtained from the Joint Research Centre (JRC) nanomaterial repository and detailed characterization has been provided by the JRC
Using representative NMs from the JRC nanomaterial repository, we have shown that THP-1 cells are more susceptible to NM-induced cell death than A549 cells

Summary

Introduction

Nanotoxicology is a scientific discipline aimed at assessing the potential adverse effects of engineered nanomaterials (NMs) as well as enabling the safe use of NMs [1].Nanotoxicology research has made great strides in the past ten to fifteen years, and efforts to pin down the mechanism(s) of NM toxicity may inform regulatory frameworks with the goal of exploiting nanotechnology in a safe and sustainable manner [2]. Nanotoxicology is a scientific discipline aimed at assessing the potential adverse effects of engineered nanomaterials (NMs) as well as enabling the safe use of NMs [1]. Much attention has been focused on the same basic paradigms, including the so-called oxidative stress paradigm [1,2]. This has certainly provided considerable insight into the biological and toxicological effects of NMs, but there may not be a one-size-fits-all mechanism with which to explain NM toxicity in different cells or tissues. The use of global omics-based approaches enables the exploration more broadly of biological mechanisms that influence the toxicity and efficacy of NMs [3].

Methods

Results

Discussion

Conclusion