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Effect of lipopolysaccharide, skin sensitizers and irritants on thioredoxin-1 expression in dendritic cells: relevance of different signalling pathways

机译:脂多糖,皮肤增敏剂和刺激物对树突状细胞中硫氧还蛋白-1表达的影响:不同信号通路的相关性

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摘要

Thioredoxin-1 is a ubiquitous protein involved in phenotypical and functional changes in dendritic cells (DC). We investigated the effect of lipopolysaccharide (LPS), skin sensitizers, and irritants on thioredoxin-1 by Western blot and immunofluorescence and on mRNA by real-time PCR. As DC models, we used a skin DC line and DC derived from human blood monocytes. We observed that all tested chemicals increased thioredoxin-1 expression, which is only transient for irritants, being the strongest effect observed for LPS (63 +/- 15%). To address the involvement of thioredoxin-1 in DC maturation, we analysed the effect of an activator of thioredoxin-1 expression, hydrogen peroxide, on CD86 expression, a marker of DC maturation. We found that hydrogen peroxide increases thioredoxin-1 and CD86 expression reinforcing thioredoxin-1 involvement in DC maturation. Because mitogen-activated protein kinases and PI3K are activated upon DC maturation, we also analysed their involvement in thioredoxin-1 modulation. We verified that LPS-induced upregulation of thioredoxin-1 expression was dependent on PI3K pathway.
机译:硫氧还蛋白-1是一种普遍存在的蛋白质,参与树突状细胞(DC)的表型和功能变化。我们通过Western印迹和免疫荧光研究了脂多糖(LPS),皮肤致敏剂和刺激物对硫氧还蛋白-1的影响,并通过实时PCR研究了其对mRNA的影响。作为DC模型,我们使用了皮肤DC线和源自人类血液单核细胞的DC。我们观察到所有测试的化学物质均增加了硫氧还蛋白-1的表达,而硫氧还蛋白-1的表达仅对刺激物是短暂的,是对LPS观察到的最强效果(63 +/- 15%)。为了解决硫氧还蛋白-1在DC成熟中的参与,我们分析了硫氧还蛋白-1表达的活化剂过氧化氢对DC成熟标志物CD86表达的影响。我们发现过氧化氢增加硫氧还蛋白-1和CD86表达加强硫氧还蛋白-1参与DC成熟。因为有丝分裂原激活的蛋白激酶和PI3K在DC成熟时被激活,所以我们还分析了它们参与硫氧还蛋白1调节的过程。我们验证了LPS诱导的硫氧还蛋白-1表达的上调依赖于PI3K途径。

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