Amorphous silica nanoparticles size-dependently aggravate atopic dermatitis-like skin lesions following an intradermal injection.

Amorphous silica nanoparticles size-dependently aggravate atopic dermatitis-like skin lesions following an intradermal injection.
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DOI:
10.1186/1743-8977-9-3
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发表时间:
2012-02-02
影响因子:
10
通讯作者:
Tsutsumi Y
Tsutsumi Y
中科院分区:
医学1区
文献类型:
--
作者:
Hirai T;Yoshikawa T;Nabeshi H;Yoshida T;Tochigi S;Ichihashi K;Uji M;Akase T;Nagano K;Abe Y;Kamada H;Itoh N;Tsunoda S;Yoshioka Y;Tsutsumi Y

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由于纳米材料(NM)的使用越来越多,人们担心NM因其独特的物理化学性质而引起不良生物效应。最近,我们报道了无定形二氧化硅纳米颗粒(nSPs),这是最广泛使用的纳米材料之一,可以穿透皮肤屏障,并诱导各种生物学效应,包括免疫调节作用。因此,应澄清nSP是否可能是皮肤免疫性疾病恶化的危险因素。因此,在这项研究中,我们研究了SP的大小和佐剂活性之间的关系,使用特应性皮炎模型。本研究观察了nSP对屋尘螨抗原(Dermatophagoides pteronyssinus,Dp)诱导的NC/Nga小鼠AD的影响。耳厚度测量和组织病理学分析表明,无定形二氧化硅颗粒(SP)和DP的组合注射诱导AD的加重,在SP的大小依赖性的方式相比,单独的DP。特别是,在注射nSP的组中观察到显著恶化。此外,这些影响与总IgE的过度诱导和更强的全身性Th 2应答相关。我们证明,这些结果与诱导IL-18和胸腺基质淋巴细胞生成素(TSLP)在皮肤病变。二氧化硅颗粒的粒径减小增强了IL-18和TSLP的产生,这导致全身性Th 2应答和由Dp抗原处理诱导的AD样皮肤病变的加重。我们认为,适当调节纳米颗粒的物理化学性质,包括尺寸,是设计更安全形式的纳米材料的关键决定因素。
Due to the rising use of nanomaterials (NMs), there is concern that NMs induce undesirable biological effects because of their unique physicochemical properties. Recently, we reported that amorphous silica nanoparticles (nSPs), which are one of the most widely used NMs, can penetrate the skin barrier and induce various biological effects, including an immune-modulating effect. Thus, it should be clarified whether nSPs can be a risk factor for the aggravation of skin immune diseases. Thus, in this study, we investigated the relationship between the size of SPs and adjuvant activity using a model for atopic dermatitis. We investigated the effects of nSPs on the AD induced by intradermaly injected-mite antigen Dermatophagoides pteronyssinus (Dp) in NC/Nga mice. Ear thickness measurements and histopathological analysis revealed that a combined injection of amorphous silica particles (SPs) and Dp induced aggravation of AD in an SP size-dependent manner compared to that of Dp alone. In particular, aggravation was observed remarkably in nSP-injected groups. Furthermore, these effects were correlated with the excessive induction of total IgE and a stronger systemic Th2 response. We demonstrated that these results are associated with the induction of IL-18 and thymic stromal lymphopoietin (TSLP) in the skin lesions. A particle size reduction in silica particles enhanced IL-18 and TSLP production, which leads to systemic Th2 response and aggravation of AD-like skin lesions as induced by Dp antigen treatment. We believe that appropriate regulation of nanoparticle physicochemical properties, including sizes, is a critical determinant for the design of safer forms of NMs.
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