Titanium Dioxide Nanoparticles Aggravate Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice

Abstract

Titanium dioxide (TiO(2)) nanoparticles are produced abundantly and used ubiquitously in various cosmetic products. However, it remains to be determined whether transdermal exposure to TiO(2) nanoparticles affects atopic dermatitis (AD), which has been increasing in developed countries. We investigated the effects of different sized TiO(2) nanoparticles on AD-like skin lesions induced to mite allergen in NC/Nga mice assumed to show skin barrier dysfunction/defect. Male mice were injected intradermally with TiO(2) nanoparticles of three sizes (15, 50, or 100 nm) and/or mite allergen into their right ears. We evaluated clinical scores, ear thickening, histological findings and the protein expression of T helper (Th) 1 and Th2 cytokines in the ear, and the levels of Ig and histamine in serum. TiO(2) nanoparticles aggravated AD-like skin lesions related to mite allergen in NC/ Nga mice. The enhancing effects are paralleled by the overproduction of IL-4 in the skin, the levels of total IgE and histamine in serum regarding the overall trend. In contrast, TiO(2) nanoparticles decreased the local expression of IFN-gamma in the presence of allergen. Additionally, TiO(2) nanoparticles alone significantly increased histamine levels in serum and IL-13 expression in the ear. However, different effects related to the size differences of TiO(2) nanoparticles were not observed. In conclusion, exposure to TiO(2) nanoparticles under skin barrier dysfunction/defect can exacerbate AD symptoms through Th2-biased immune responses. Furthermore, TiO(2) nanoparticles can play a significant role in the initiation and/or progression of skin diseases following the barrier dysfunction/defect by histamine release even in the absence of allergen.

Perturbation of physiological systems by nanoparticles

“…351 Although nanoparticle-induced atopic dermatitis has not been reported, some nanoparticles, including TiO 2 , polystyrene, and amorphous SiO 2 nanoparticles, exacerbate atopic dermatitis by acting as allergens after intradermal injection. [352][353][354] This activity may further enhance the excessive induction of total IgE and cause a stronger systemic Th2 response. 354 Phototoxicity describes an inflammatory skin reaction that results from the topical application of chemical substances and subsequent exposure to light, particularly ultraviolet A radiation (320-400 nm).…”

Immunotoxicity of zinc oxide nanoparticles with different size and electrostatic charge

“…In addition, in vitro exposure of ZnO leads to generation of reactive oxygen species (ROS), upregulation of genes involved in apoptosis, and cell death in human keratinocyte HaCaT cells. 13,14 Likewise, profuse release of inflammatory mediators induced by ZnO NPs 15,16 may result in immune stimulation or aggravation of immune diseases 17 or even break down T helper (Th)-1/Th-2 balance. 18 It is well known that immunotoxicity of NPs is intimately linked to oxidative stress.…”

ESR and XRD investigation of effects induced by gamma radiation on PVA-TiO2 membranes

“…The doped PVA mem-branes with TiO 2 are used in the photocatalytic degradation of ethanol, [12], and cross linked PVA containing TiO 2 nanoparticles are used for humidity sensors, [13]. In medicine TiO 2 is introduced into the polymeric matrix in order to reduce the penetration of UV radiation, but also for its antimicrobial action, [14][15][16][17].…”