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

药物光过敏反应或药物过敏反应体外替代检查的发展

基本信息

批准号：
22590543
负责人：
BITO Toshinori
金额：
$ 2.83万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590543/
关键词：
アレルギー光アレルギー表皮細胞金属リンパ球刺激試験

项目摘要

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

应用免疫组化方法检测了H_2O_2对健康志愿者皮肤细胞信号转导子和转录激活子3（Stat 3）的影响。国际劳工局警告说，皮肤或粘膜接触过氧化氢（H_2O_2）会引起严重的炎症变化。当皮肤暴露于35%H_2O_2时，可出现红斑、紫癜，甚至皮下气肿，有几例病例报道。H_2O_2的浓度和暴露时间对皮肤的影响尚不清楚。Stat 3对外部应激的反应拯救受损细胞免于凋亡，因为在人淋巴细胞中已经观察到Stat 3通过氧化应激活化。然而，目前还没有关于Stat 3和人体皮肤氧化应激的数据。本文研究了H_2O_2对健康志愿者皮肤损害的影响 ...更多信息对于Stat 3的执行情况。我们的研究还表明Stat 3的激活是H_2O_2损伤的一个很好的标志。我们最近发现H_2O_2直接磷酸化人表皮角质形成细胞和成纤维细胞中的Stat 3蛋白，而不介导膜受体或细胞因子。本研究中观察到的结果与体外数据一致。因此，在H_2O_2暴露的皮肤中，Stat 3的激活先于临床和组织学变化，当细胞受到严重损伤时，如在30%H_2O_2暴露10或30 min时，磷酸化Stat 3蛋白消失。我们在《皮肤科学杂志》上发表了这一数据。此外，我们通过使用THP-1淋巴细胞体外试验评价了酮洛芬（已知为光敏剂）的致敏性和光致敏性，并证明了对评价材料毒性和致敏性的部分有用性。这些数据在职业与环境健康大学第28届年会上公布。少