γ-Tocotrienol Reduces Squalene Hydroperoxide-Induced Inflammatory Responses in HaCaT Keratinocytes
γ-Tocotrienol Reduces Squalene Hydroperoxide-Induced Inflammatory Responses in HaCaT Keratinocytes
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DOI：
10.1007/s11745-010-3458-4
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发表时间：
2010-09-01
期刊：
影响因子：
1.9
通讯作者：
Miyazawa, Teruo
中科院分区：
文献类型：
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作者：
Nakagawa, Kiyotaka;Shibata, Akira;Miyazawa, Teruo
角鲨烯氢过氧化物（SQ- ooh）是角鲨烯（SQ）的主要过氧化产物，在暴露于阳光下的人体皮肤表面积累。然而，关于SQ-OOH的致病作用（即炎症刺激）的研究却很少。在这里，我们评估了SQ-OOH是否在永活的人角质形成细胞（HaCaT）中诱导炎症反应。我们发现SQ-OOH引起炎症基因如白细胞介素和环氧化酶-2 （COX-2）的表达增加。与COX-2 mRNA的上调一致，SQ-OOH增强了活性氧的产生、核因子κ B的激活、COX-2蛋白的表达和前列腺素E2的产生。因此，SQ-OOH的促炎作用可能部分是通过COX-2介导的。另一方面，γ -生育三烯醇（γ - t3，维生素E的一种不饱和形式）被发现可以改善SQ-OOH的作用。这些结果表明，SQ-OOH在HaCaT中诱导炎症反应，表明SQ-OOH在炎症性皮肤病中起重要作用。作为一种预防策略，可以通过使用γ - t3来减少炎症。
Squalene hydroperoxide (SQ-OOH), the primary peroxidation product of squalene (SQ), accumulates at the surface of sunlight-exposed human skin. There are however only a few studies on the pathogenic actions (i.e., inflammatory stimuli) of SQ-OOH. Here, we evaluated whether SQ-OOH induced inflammatory responses in immortalized human keratinocytes (HaCaT). We found that SQ-OOH caused an increase in the expression of inflammatory genes such as the interleukins as well as cyclooxygenase-2 (COX-2). In concordance with the upregulation of COX-2 mRNA, SQ-OOH enhanced reactive oxygen species generation, nuclear factor kappa B activation, COX-2 protein expression, and prostaglandin E2 production. Therefore, the pro-inflammatory effects of SQ-OOH may be mediated in part via COX-2. On the other hand, gamma-tocotrienol (gamma-T3, an unsaturated form of vitamin E) was found to ameliorate the SQ-OOH actions. These results suggest that SQ-OOH induces inflammatory responses in HaCaT, implying that SQ-OOH plays an important role in inflammatory skin disorders. As a preventive strategy, inflammation could be reduced via the use of gamma-T3.