Development of in vitro alternative examination for drug-induced photo-allergic reaction or drug-induced allergic reaction

我们用免疫组化方法研究了健康志愿者皮肤损伤发生所需的h_2o_2浓度和暴露时间。国际劳工组织警告说，高浓度过氧化氢（H_2O_2）与皮肤或粘膜接触会导致严重的炎症变化。当皮肤暴露于35% H_2O_2时，可发生红斑、紫癜，甚至皮下肺气肿。目前尚不清楚h_2o_2的浓度是多少，暴露在h_2o_2中多长时间会引起皮肤变化。Stat3对外部应激的反应拯救了受损细胞免于凋亡，因为在人类淋巴细胞中观察到Stat3通过氧化应激激活。然而，尚无关于人体皮肤中Stat3和氧化应激的数据。在此，我们研究了免疫组织健康志愿者皮肤损伤发生所需的h_2o_2浓度和暴露时间。我们的研究还表明Stat3活化是h_2o_2损伤的一个很好的标志。我们最近证明h_2o_2直接磷酸化Stat3蛋白，而不介导人表皮角质形成细胞和成纤维细胞的膜受体或细胞因子。本研究结果与体外实验结果一致。因此，在暴露于H_2O_2的皮肤中，Stat3的激活先于临床和组织学变化，并且在暴露于30% H_2O_2 10 min或30 min时，当细胞严重损伤时，磷酸化-Stat3蛋白消失。我们在《皮肤科学杂志》上发表了这一数据。此外，我们还通过体外THP-1淋巴细胞实验对光敏剂酮洛芬的致敏性和光致敏性进行了评价，并证明了对材料毒性和致敏性评价的部分有用性。这些数据发表在职业与环境健康大学的第28届年会上。少

We investigated the concentration and exposure time of H_2O_2necessary for the development of skin damage in healthy volunteers with immunohistochemistry for signal transducer and activator of transcription3 (Stat3). The International Labour Office has warned that contact of concentrated hydrogen peroxide (H_2O_2) with skin or mucosa can cause severe inflammatory changes. When the skin is exposed to 35% H_2O_2, erythema, purpura, and even subcutaneous emphysema may occur,as documented in several case reports. It remains unknown how much concentration of H_2O_2and how long exposure to it evokes skin changes. Stat3 response to outer stress rescues the damaged cells from apoptosis, as Stat3 activation through oxidative stress has been observed in human lymphocytes. However, there has been no data on Stat3 andoxidative stress in human skin. Here we investigated the concentration and exposure time of H_2O_2necessary for the development of skin damage in healthy volunteers with immunohistoch … More emistry for Stat3. Our study also demonstrated that Stat3 activation is a good hallmark for H_2O_2damage. We have recently demonstrated that H_2O_2directly phosphorylates Stat3 protein without mediating membrane receptors or cytokines in human epidermal keratinocytes and fibroblasts. The observation seen in this study is consistent with those in vitrodata. Thus, Stat3 activation precedes the clinical and histological changes in the H_2O_2-exposed skin, and phosopho-Stat3 protein disappeared when the cells were seriously damaged as seen in 10 or 30 min-exposure to 30% H_2O_2. We published this data on the Journal of Dermatological Science. In addition, we have evaluated the allergenicity and photo-allergenicity of ketoprofen, which is known as a photo-sensitizing agent, by using THP-1 lymphocytes in vitro assay, and have demonstrated the partial usefulness for the evaluation of toxicity and allergenicity of the materials. The data were presented at 28thannual meeting of University of Occupational and EnvironmentalHealth. Less