Wu Shuling, Gao Jianping, Dinh Q Thai, Chen Christiane, Fimmel Sabine
Medicine Clinic III, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, Germany.
Mol Immunol. 2008 Apr;45(8):2288-96. doi: 10.1016/j.molimm.2007.11.019. Epub 2008 Feb 21.
Identification of individual response-signal pathway induced by UVA-irradiation is necessary for understanding photo-biological and -pathological mechanisms with respect to the prevention of UV-irradiated skin damage and aging. Here, we investigated the role of D-alpha-tocopherol in the regulation of IL-8 production and AP-1 binding activity in UVA-irradiated human keratinocytes. UVA dramatically upregulated IL-8 mRNA expression and protein secretion and enhanced the AP-1-DNA binding activity. These effects of UVA irradiation were effectively reduced by D-alpha-tocopherol in a dose-dependent manner. The human keratinocytes expressed various NAD(P)H oxidase components, gp91phox homologues Nox1, and p22phox, p47phox, p67phox, as well as NOXO1, suggesting that cellular stress induced by UVA included the activation of non-phagocytic NADPH oxidase system, leading to AP-1 transactivation and IL-8 expression. D-alpha-tocopherol significantly inhibited the NADPH oxidase activity and the formation of malondialdehyde-thiobarbituric acid under UVA exposure. These results demonstrated that D-alpha-tocopherol may be able to prevent the IL-8 upregulation and the increase in AP-1 activation induced by UVA irradiation through down-modulating cellular oxidative stress.
识别由紫外线A（UVA）照射诱导的个体反应信号通路，对于理解预防紫外线照射引起的皮肤损伤和衰老的光生物学及病理机制是必要的。在此，我们研究了D-α-生育酚在调节UVA照射的人角质形成细胞中白细胞介素-8（IL-8）产生和激活蛋白-1（AP-1）结合活性方面的作用。UVA显著上调IL-8 mRNA表达和蛋白分泌，并增强AP-1与DNA的结合活性。D-α-生育酚以剂量依赖的方式有效降低了UVA照射的这些效应。人角质形成细胞表达各种烟酰胺腺嘌呤二核苷酸磷酸（NAD(P)H）氧化酶成分、gp91phox同源物Nox1以及p22phox、p47phox、p67phox，还有NOXO1，这表明UVA诱导的细胞应激包括非吞噬性NADPH氧化酶系统的激活，导致AP-1反式激活和IL-8表达。D-α-生育酚在UVA照射下显著抑制NADPH氧化酶活性和丙二醛-硫代巴比妥酸的形成。这些结果表明，D-α-生育酚可能能够通过下调细胞氧化应激来预防UVA照射诱导的IL-8上调和AP-1激活增加。
