Titanium dioxide (TiO2) nanoparticles are produced abundantly and used ubiquitously in various cosmetic products. However, it remains to be determined whether transdermal exposure to TiO2 nanoparticles affects atopic dermatitis (AD), which has been increasing in developed countries. We investigated the effects of different sized TiO2 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 TiO2 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. TiO2 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, TiO2 nanoparticles decreased the local expression of IFN-γ in the presence of allergen. Additionally, TiO2 nanoparticles alone significantly increased histamine levels in serum and IL-13 expression in the ear. However, different effects related to the size differences of TiO2 nanoparticles were not observed. In conclusion, exposure to TiO2 nanoparticles under skin barrier dysfunction/defect can exacerbate AD symptoms through Th2-biased immune responses. Furthermore, TiO2 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.
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