Nakagawa Kiyotaka, Shibata Akira, Maruko Toru, Sookwong Phumon, Tsuduki Tsuyoshi, Kawakami Kayoko, Nishida Hiroshi, Miyazawa Teruo
Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan.
Lipids. 2010 Sep;45(9):833-41. doi: 10.1007/s11745-010-3458-4. Epub 2010 Aug 17.
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.
角鲨烯过氧化氢（SQ - OOH）是角鲨烯（SQ）的主要过氧化产物，在暴露于阳光的人体皮肤表面积累。然而，关于SQ - OOH致病作用（即炎症刺激）的研究却很少。在此，我们评估了SQ - OOH是否会在永生化人角质形成细胞（HaCaT）中诱导炎症反应。我们发现，SQ - OOH导致炎症基因如白细胞介素以及环氧化酶 - 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κB的激活、COX - 2蛋白的表达以及前列腺素E2的产生。因此，SQ - OOH的促炎作用可能部分通过COX - 2介导。另一方面，发现γ-生育三烯酚（γ-T3，维生素E的一种不饱和形式）可改善SQ - OOH的作用。这些结果表明，SQ - OOH在HaCaT中诱导炎症反应，这意味着SQ - OOH在炎症性皮肤病中起重要作用。作为一种预防策略，可通过使用γ-T3减轻炎症。
