Size Effects of Polystyrene Nanoparticles on Atopic Dermatitis-like Skin Lesions in NC/NGA Mice

Abstract

Nano-sized particles are diffusing in the environment with the development of nanotechnology. Polystyrene (PS) nanoparticles are modified industrial products and pharmaceutical agents, however, adverse effects of PS nanoparticles remain to be elucidated. In the present study, we investigated the effects of PS nanoparticles with different sizes on the atopic dermatitis (AD)-like skin lesions in NC/Nga mice assumed to show the skin barrier defect/dysfunction in the presence or absence of mite allergen. Male NC/Nga mice were injected intradermally with three different-sized PS nanoparticles (25, 50, or 100 nm) and/or mite allergen into their right ears. We evaluated clinical scores, ear thickening, histological findings and the local protein expression of inflammatory molecules in the ear and Ig production in serum. PS nanoparticles aggravated AD-like skin lesions related to mite allergen, which was paralleled by the local protein levels of interleukin-4, CCL2/monocyte chemotactic protein-1, CCL3/macrophage inflammatory protein-1 alpha, and CCL4/macrophage inflammatory protein-1 beta. In contrast, PS nanoparticles decreased interferon-gamma expression. Furthermore, exposure to PS nanoparticles induced ear swelling and CC-chemokine expression in the absence of allergen. These effects were greater with the smaller PS nanoparticles than with the larger ones regarding overall trend. These results suggest that exposure to PS nanoparticles under skin barrier defect/dysfunction can exacerbate AD-like skin lesions related to mite allergen in a size-dependent manner. The enhancing effects may be accounted for by T helper 2-biased immune responses. Furthermore, PS nanoparticles can evoke skin inflammation via the overexpression of CC-chemokines even in the absence of allergen in atopic subjects.