Green tea polyphenols prevent UV-induced immunosuppression by rapid repair of DNA damage and enhancement of nucleotide excision repair genes.
Green tea polyphenols prevent UV-induced immunosuppression by rapid repair of DNA damage and enhancement of nucleotide excision repair genes.
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DOI：
10.1158/1940-6207.capr-09-0044
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发表时间：
2010-02
期刊：
影响因子：
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通讯作者：
Meeran SM
中科院分区：
文献类型：
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作者：
Katiyar SK;Vaid M;van Steeg H;Meeran SM
紫外线（UV）辐射诱导的免疫抑制与皮肤癌的发展有关。由于口服饮用水中的绿色茶多酚（GTP）可预防小鼠的光致癌作用，我们研究了饮用水中的GTP（0.1- 0.5%，w/v）是否可预防UV诱导的免疫抑制，并确定了GTP的可能作用机制。我们观察到GTP（0.2和0.5%，w/v）在局部（58- 62%，p<0.001）和全身（51- 55%，p<0.005）接触超敏反应（CHS）模型中阻止了UV诱导的对接触致敏剂的接触超敏反应（CHS）抑制。GTP（0.2%，w/v）可更快地修复小鼠皮肤中UV诱导的DNA损伤，如环丁烷嘧啶二聚体（CPD）阳性细胞数量减少（59%，p<0.001）所示，并减少CPD阳性细胞从皮肤向引流淋巴结的迁移（2倍），这与核苷酸切除修复（NER）基因水平升高有关。GTP不能阻止NER缺陷小鼠中UV诱导的免疫抑制，但能显著阻止NER熟练小鼠中UV诱导的免疫抑制（p<0.001），同时修复NER熟练小鼠中UV诱导的DNA损伤（p<0.001），但对CPD阳性细胞的免疫组织化学分析表明，GTP不能阻止NER缺陷小鼠中UV诱导的DNA损伤。Southwestern dot-blot分析显示，GTP修复了从健康人获得的着色性干皮病互补组A（XPA）-熟练细胞中UV诱导的CPD，但在从患有XPA的患者获得的XPA-缺陷细胞中没有修复，表明NER机制参与DNA修复。这些数据确定了一个高贵的机制，饮用GTP防止紫外线诱导的免疫抑制，这可能有助于GTP的化学预防活性，在预防光致癌。
Ultraviolet (UV) radiation-induced immunosuppression has been implicated in the development of skin cancers. As oral administration of green tea polyphenols (GTPs) in drinking water prevents photocarcinogenesis in mice, we studied whether administration of GTPs in drinking water of mice (0.1-0.5%, w/v) prevents UV-induced immunosuppression, and determined the possible mechanism of action of GTPs. We observed that GTPs (0.2 and 0.5%, w/v) prevented UV-induced suppression of contact hypersensitivity (CHS) response to a contact sensitizer in local (58-62%, p<0.001) and systemic (51-55%, p<0.005) models of CHS. GTPs (0.2%, w/v) repaired UV-induced DNA damage faster in the skin of mice as demonstrated by reduced number of cyclobutane pyrimidine dimers (CPD)-positive cells (59%, p<0.001), and reduced the migration of CPD-positive cells (2-fold) from the skin to draining lymph nodes, which was associated with the elevated levels of nucleotide excision repair (NER) genes. GTPs did not prevent UV-induced immunosuppression in NER-deficient mice but significantly prevented in NER-proficient mice (p<0.001) concomitantly repaired UV-induced DNA damage in NER-proficient mice (p<0.001) but not in NER-deficient mice as indicated by immunohistochemical analysis of CPD-positive cells. Southwestern dot-blot analysis revealed that GTPs repaired UV-induced CPD in xeroderma pigmentosum complementation group A (XPA)-proficient cells obtained from healthy person but did not repair in XPA-deficient cells obtained from the patients suffering from XPA, indicating that NER mechanism is involved in DNA repair. These data identify a noble mechanism by which drinking GTPs prevent UV-induced immunosuppression, and this may contribute to the chemopreventive activity of GTPs in prevention of photocarcinogenesis.