Suppression of UVB-induced phosphorylation of mitogen-activated protein kinases and nuclear factor kappa B by green tea polyphenol in SKH-1 hairless mice
Suppression of UVB-induced phosphorylation of mitogen-activated protein kinases and nuclear factor kappa B by green tea polyphenol in SKH-1 hairless mice
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DOI：
10.1038/sj.onc.1207035
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发表时间：
2003-12-18
期刊：
影响因子：
8
通讯作者：
Mukhtar, H
中科院分区：
文献类型：
--
作者：
Afaq, F;Ahmad, N;Mukhtar, H
我们实验室的研究表明，绿茶中存在的主要多酚Epigalocatechin-3-Gallate抑制其紫外线（UV）B-暴露于丝分裂原活化蛋白激酶（MAPKS）（Toxicol。Appl。176Pharmacol。176）的紫外线（UV）B-暴露介导的磷酸化。176 ：110-117，2001）和核因子Kappa B（NF-kappab）的激活（Oncogene） 22：1035-1044,2003）正常人表皮角质形成细胞中的途径。这项研究旨在研究这些发现与SKH-1无毛小鼠模型中体内情况的相关性，该模型被认为与人类情况有关。 SKH-1无毛小鼠用GTP（5 mg/0.2 ml丙酮/小鼠）局部处理，并在30分钟后暴露于UVB（180 mJ/cm（2））。每天的每一天重复两周，共七个治疗方法，共有7种治疗方法。上次UVB暴露后24小时，动物被杀死。 GTP的局部应用导致UVB诱导的双子皮肤厚度，皮肤水肿和白细胞浸润显着降低。采用蛋白质印迹分析和免疫组织化学研究，我们发现GTP导致UVB诱导的抑制：（i）磷酸化细胞外信号调节的激酶（ERK1/2）（ERK1/2），（II）C-JUN N-末端激酶和（（II） iii）p38蛋白表达。由于NF-kappab在炎症和细胞增殖中起主要作用，因此我们评估了GTP对NF-kappab途径中UVB介导的调制的影响。我们的数据表明，GTP抑制了UVB诱导的：（i）NF-kappab的激活，（ii）ikkalpha的激活和（iii）Ikappabalpha的磷酸化和降解。我们的数据表明，GTP可以通过MAPK和NF-kappab信号通路中的调制来预防紫外线辐射的不利影响，并为GTP在体内动物模型系统中的光化学重新预防效应提供了分子基础。
Studies from our laboratory have shown that epigallocatechin-3-gallate, the major polyphenol present in green tea, inhib its ultraviolet (UV)B-exposure-mediated phosphorylation of mitogen-activated protein kinases (MAPKs) (Toxicol. Appl. Pharmacol. 176: 110-117, 2001) and activation of nuclear factor kappa B (NF-kappaB) (Oncogene 22: 1035-1044,2003) pathways in normal human epidermal keratinocytes. This study was designed to investigate the relevance of these findings to the in vivo situations in SKH-1 hairless mouse model, which is regarded to have relevance to human situations. SKH-1 hairless mice were topically treated with GTP (5 mg/0.2 ml acetone/mouse) and were exposed to UVB 30 min later (180 mJ/cm(2)). These treatments were repeated every alternate day for 2 weeks, for a total of seven treatments. The animals were killed 24 h after the last UVB exposure. Topical application of GTP resulted in significant decrease in UVB-induced bifold-skin thickness, skin edema and infiltration of leukocytes. Employing Western blot analysis and immunohistochemical studies, we found that GTP resulted in inhibition of UVB-induced: (i) phosphorylation of extracellular-signal-regulated kinases (ERK1/2),(ii) c-Jun N-terminal kinases, and (iii) p38 protein expression. Since NF-kappaB plays a major role in inflammation and cell proliferation, we assessed the effect of GTP on UVB-mediated modulations in the NF-kappaB pathway. Our data demonstrated that GTP inhibited UVB-induced: (i) activation of NF-kappaB,(ii) activation of IKKalpha, and (iii) phosphorylation and degradation of IkappaBalpha. Our data suggest that GTP protects against the adverse effects of UV radiation via modulations in MAPK and NF-kappaB signaling pathways, and provides molecular basis for the photochemopreventive effect of GTP in an in vivo animal model system.