Lack of transient receptor potential melastatin 8 activation by phthalate esters that enhance contact hypersensitivity in mice
Lack of transient receptor potential melastatin 8 activation by phthalate esters that enhance contact hypersensitivity in mice
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DOI：
10.1016/j.toxlet.2012.12.025
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发表时间：
2013-03-13
影响因子：
3.5
通讯作者：
Imai, Yasuyuki
中科院分区：
文献类型：
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作者：
Kurohane, Kohta;Sahara, Yurina;Imai, Yasuyuki
我们使用小鼠模型研究了感觉神经元参与皮肤对过敏原的致敏作用，其中辅助性T细胞2型反应是必不可少的。皮肤对异硫氰酸荧光素（FITC）的致敏性已被证明是由几种邻苯二甲酸酯，包括邻苯二甲酸二丁酯（DBP）增强。对于不同类型的邻苯二甲酸酯，我们发现瞬时受体电位（TRP）A1激活的能力和增强皮肤致敏的能力之间的相关性。TRPA 1特异性拮抗剂HC-030031显示在DBP存在下抑制皮肤致敏。然而，由于邻苯二甲酸酯也激活TRPV 1，邻苯二甲酸酯可以非选择性地激活其他类型的TRP通道。此外，薄荷脑还可以增强对FITC的致敏作用，从而激活TRPA 1和TRPM 8。在这里，我们建立了一个体外系统，用于测量TRPM 8激活。通过两种TRPM 8激动剂（薄荷醇和icilin）诱导钙动员，而TRPA 1和TRPV 1激动剂不诱导钙动员的事实确定了对TRPM 8的选择性。我们证明了邻苯二甲酸酯不会激活TRPM 8。TRPA 1拮抗剂HC-030031不抑制薄荷醇或icilin诱导的TRPM 8活化。这些结果表明，邻苯二甲酸酯选择性地活化TRPA 1和TRPV 1。TRPM 8激活不太可能参与对FITC的致敏作用。(C)2013爱思唯尔爱尔兰有限公司版权所有。
We studied the involvement of sensory neurons in skin sensitization to allergens using a mouse model in which the T-helper type 2 response is essential. Skin sensitization to fluorescein isothiocyanate (FITC) has been shown to be enhanced by several phthalate esters, including dibutyl phthalate (DBP). For different types of phthalate esters, we found a correlation between the ability of transient receptor potential (TRP) A1 activation and that of enhancing skin sensitization. A TRPA1-specific antagonist, HC-030031, was shown to suppress skin sensitization in the presence of DBP. However, since phthalate esters also activate TRPV1, phthalate esters could activate other types of TRP channels non-selectively. Furthermore, sensitization to FITC is also enhanced by menthol, which activates TRPA1 and TRPM8. Here we established an in vitro system for measuring TRPM8 activation. The selectivity for TRPM8 was established by the fact that two TRPM8 agonists (menthol and icilin) induced calcium mobilization, whereas agonists of TRPA1 and TRPV1 did not. We demonstrated that phthalate esters do not activate TRPM8. TRPA1-antagonist HC-030031 did not inhibit TRPM8 activation induced by menthol or icilin. These results show that phthalate esters activate TRPA1 and TRPV1 with selectivity. TRPM8 activation is not likely to be involved in the sensitization to FITC. (C) 2013 Elsevier Ireland Ltd. All rights reserved.