Yanagisawa Rie, Takano Hirohisa, Inoue Ken-Ichiro, Koike Eiko, Kamachi Tomoko, Sadakane Kaori, Ichinose Takamichi
Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan.
Exp Biol Med (Maywood). 2009 Mar;234(3):314-22. doi: 10.3181/0810-RM-304. Epub 2009 Jan 14.
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.
二氧化钛（TiO₂）纳米颗粒产量巨大，在各种化妆品中广泛使用。然而，经皮暴露于TiO₂纳米颗粒是否会影响特应性皮炎（AD）仍有待确定，而在发达国家，特应性皮炎的发病率一直在上升。我们研究了不同尺寸的TiO₂纳米颗粒对假定存在皮肤屏障功能障碍/缺陷的NC/Nga小鼠因螨过敏原诱发的类AD皮肤损伤的影响。将三种尺寸（15、50或100 nm）的TiO₂纳米颗粒和/或螨过敏原皮内注射到雄性小鼠的右耳。我们评估了临床评分、耳部增厚、组织学结果以及耳部辅助性T细胞（Th）1和Th2细胞因子的蛋白表达，以及血清中Ig和组胺水平。TiO₂纳米颗粒加重了NC/Nga小鼠中与螨过敏原相关的类AD皮肤损伤。在总体趋势上，皮肤中IL-4的过度产生、血清中总IgE和组胺水平的升高与这种增强作用平行。相比之下，在存在过敏原的情况下，TiO₂纳米颗粒降低了IFN-γ的局部表达。此外，单独的TiO₂纳米颗粒显著增加了血清中的组胺水平以及耳部IL-13的表达。然而，未观察到与TiO₂纳米颗粒尺寸差异相关的不同影响。总之，在皮肤屏障功能障碍/缺陷的情况下暴露于TiO₂纳米颗粒可通过偏向Th2的免疫反应加剧AD症状。此外，即使在没有过敏原的情况下，TiO₂纳米颗粒也可通过组胺释放，在屏障功能障碍/缺陷后的皮肤疾病的起始和/或进展中发挥重要作用。
