Sonicated and stirred copper oxide nanoparticles induce similar toxicity and pro-inflammatory response in N-hTERT keratinocytes and SZ95 sebocytes
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The potential toxic and pro-inflammatory effects of rod-shaped copper oxide (CuO) nanoparticles (NPs; 10 ± 3 nm in thickness and 74 ± 17 nm in length) were studied on N-hTERT keratinocytes and SZ95 sebocytes and on reconstructed human epidermis. Non-sonicated and sonicated CuO NPs induced similar cellular toxicity. The toxic effect of CuO NPs (non-sonicated and sonicated) was more pronounced in keratinocytes than in sebocytes. Pro-oxidant effects of CuO NPs were demonstrated by showing increase in the production of reactive oxygen species and decrease of cellular glutathione. In addition, DNA-binding activities suggested that redox-sensitive transcription factors Nrf2 and NF-κB were implicated in the response of keratinocytes to CuO NPs. Transcriptomic analysis showed an increase in the abundance of transcript species coding for pro-inflammatory interleukins (e.g. IL-8 and IL-1α) and chemokines. In reconstituted human epidermis exposed topically to raw CuO NPs, no effect on the integrity, viability and inflammatory response was noticed.
KeywordsCopper oxide nanoparticles Sonication Sebocytes Keratinocytes Toxicity Inflammatory response
This work was supported by the DGO6 (Direction Générale Opérationnelle de l’Economie, de l’Emploi et de la Recherche) of the Walloon Region of Belgium (‘Nanotoxico’ Pole of Excellence, 516252). The research leading to these results has received funding from the European Commission Seventh Framework Programme (FP7/2007-2013) under Grant Agreement No. 262163 (QualityNano infrastructure). O. Toussaint is a Senior Research Associate of the Belgian FNR/FNRS.
Conflict of interest
The authors declare that there are no conflicts of interest.
- Bertrand-Vallery V, Belot N, Dieu M, Delaive E, Ninane N, Demazy C, Raes M, Salmon M, Poumay Y, Debacq-Chainiaux F, Toussaint O (2010a) Proteomic profiling of human keratinocytes undergoing UVB-induced alternative differentiation reveals TRIpartite Motif Protein 29 as a survival factor. PLoS One 5(5):e10462CrossRefGoogle Scholar
- Briviba K, Klotz LO, Sies H (1997) Toxic and signaling effects of photochemically or chemically generated singlet oxygen in biological systems. Biol Chem 378(11):1259–1265Google Scholar
- Cohen D, Soroka Y, Ma’or Z, Oron M, Portugal-Cohen M, Bregegere FM, Berhanu D, Valsami-Jones E, Hai N, Milner Y (2012) Evaluation of topically applied copper(II) oxide nanoparticle cytotoxicity in human skin organ culture. Toxicol In Vitro 27(1):292–298. doi: 10.1016/j.tiv.2012.08.026 CrossRefGoogle Scholar
- Coquette A, Berna N, Vandenbosch A, Rosdy M, De Wever B, Poumay Y (2003) Analysis of interleukin-1alpha (IL-1alpha) and interleukin-8 (IL-8) expression and release in in vitro reconstructed human epidermis for the prediction of in vivo skin irritation and/or sensitization. Toxicol In Vitro 17(3):311–321CrossRefGoogle Scholar
- Dickson MA, Hahn WC, Ino Y, Ronfard V, Wu JY, Weinberg RA, Louis DN, Li FP, Rheinwald JG (2000) Human keratinocytes that express hTERT and also bypass a p16(INK4a)-enforced mechanism that limits life span become immortal yet retain normal growth and differentiation characteristics. Mol Cell Biol 20(4):1436–1447CrossRefGoogle Scholar
- Kunsch C, Rosen CA (1993) NF-kappa B subunit-specific regulation of the interleukin-8 promoter. Mol Cell Biol 13(10):6137–6146Google Scholar
- Mortimer M, Kasemets K, Kahru A (2009) Toxicity of ZnO and CuO nanoparticles to ciliated protozoa Tetrahymena thermophila. Toxicology 269(2–3):182–189Google Scholar
- Mroz RM, Schins RP, Li H, Drost EM, Macnee W, Donaldson K (2007) Nanoparticle carbon black driven DNA damage induces growth arrest and AP-1 and NFkappaB DNA binding in lung epithelial A549 cell line. J Physiol Pharmacol 58 Suppl 5(Pt 2):461–470Google Scholar
- Oberdorster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, Carter J, Karn B, Kreyling W, Lai D, Olin S, Monteiro-Riviere N, Warheit D, Yang H (2005) Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol 2:8CrossRefGoogle Scholar
- Piret JP, Jacques D, Audinot JN, Mejia J, Boilan E, Noel F, Fransolet M, Demazy C, Lucas S, Saout C, Toussaint O (2012a) Copper (II) oxide nanoparticles penetrate into HepG2 cells, exert cytotoxicity via oxidative stress and induce pro-inflammatory response. Nanoscale 4:7168–7184CrossRefGoogle Scholar
- Piret JP, Vankoningsloo S, Mejia J, Noel F, Boilan E, Lambinon F, Zouboulis CC, Masereel B, Lucas S, Saout C, Toussaint O (2012b) Differential toxicity of copper (II) oxide nanoparticles of similar hydrodynamic diameter on human differentiated intestinal Caco-2 cell monolayers is correlated in part to copper release and shape. Nanotoxicology 6(7):789–803CrossRefGoogle Scholar
- Vankoningsloo S, De Pauw A, Houbion A, Tejerina S, Demazy C, de Longueville F, Bertholet V, Renard P, Remacle J, Holvoet P, Raes M, Arnould T (2006) CREB activation induced by mitochondrial dysfunction triggers triglyceride accumulation in 3T3-L1 preadipocytes. J Cell Sci 119(Pt 7):1266–1282CrossRefGoogle Scholar
- Vankoningsloo S, Piret JP, Saout C, Noel F, Mejia J, Zouboulis CC, Delhalle J, Lucas S, Toussaint O (2010) Cytotoxicity of multi-walled carbon nanotubes in three skin cellular models: effects of sonication, dispersive agents and corneous layer of reconstructed epidermis. Nanotoxicology 4(1):84–97CrossRefGoogle Scholar
- Vankoningsloo S, Piret JP, Saout C, Noel F, Mejia J, Coquette A, Zouboulis CC, Delhalle J, Lucas S, Toussaint O (2012) Pro-inflammatory effects of different MWCNTs dispersions in p16(INK4A)-deficient telomerase-expressing human keratinocytes but not in human SV-40 immortalized sebocytes. Nanotoxicology 6(1):77–93CrossRefGoogle Scholar