Analysis of the Activation Routes Induced By Different Metal Oxide Nanoparticles On Human Lung Epithelial Cells

Abstract

Nanoparticles (Nps) can induce toxicity in the lung by accidental or intentional exposure. The main objective of the study reported here was to characterize the effect that four metal oxide Nps (CeO₂, TiO₂, Al₂O₃ and ZnO) had at the cellular level on a human lung epithelial cell line. This goal was achieved by studying the capacity of the Nps to activate the main mitogen-activated protein kinases (MAPKs) and the nuclear factor NFκB. Only ZnO Nps were able to activate all of the MAPKs and the release of Zn²⁺ ions was the main cause of activation. ZnO and Al₂O₃ Nps activated the NFκB pathway and induced the release of inflammatory cytokines. CeO₂ and TiO₂ Nps were found to have safer profiles.

The graphical abstract was obtained using Servier Medical Art.

Lay abstract: When cells are exposed to a stimulus, they can activate different signaling pathways and these lead to different responses such as proliferation, differentiation, migration or inflammation. The objective of the work described here was to characterize the effects of several metal oxide nanoparticles at the cellular level by studying their capacity to activate the main mitogen-activated protein kinases (MAPKs) and the expression of the transcription factor NFκB on a human lung epithelial cell line. These signaling proteins play a relevant role in the vast majority of the cellular events that are triggered in eukaryotic cells after any stimulus.

Keywords::

• cytokines
• inflammation
• MAPK
• metal oxide nanoparticles
• NFκB

Supplemental Material

Financial & competing interests disclosure

This work was supported by the HINAMOX project (228825, FP7-NMP-SMALL-2) and the Xunta de Galicia (INBIOMED 2012/273, DXPCTSUG-FEDER, Grupo de Potencial de Crecimiento GPC2013-005). We also thank the BIOCAPS project (316265, FP7/REGPOT-2012–2013.1) and T Lozano-Fernández acknowledges an FPU fellowship (Spanish Ministry of Education). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.