Prevention of UVB-induced immunosuppression in mice by the green tea polyphenol (-)-epigallocatechin-3-gallate may be associated with alterations in IL-10 and IL-12 production
Prevention of UVB-induced immunosuppression in mice by the green tea polyphenol (-)-epigallocatechin-3-gallate may be associated with alterations in IL-10 and IL-12 production
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DOI：
10.1093/carcin/20.11.2117
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发表时间：
1999-11-01
期刊：
影响因子：
4.7
通讯作者：
Mukhtar, H
中科院分区：
文献类型：
--
作者：
Katiyar, SK;Challa, A;Mukhtar, H
皮肤暴露在紫外线下，特别是紫外线(290-320 nm)，会引起不良的生物效应，包括皮肤免疫细胞的改变、光老化和光致癌。几项研究表明，从绿茶中分离出的多酚类化合物对UVB诱导的炎症反应和小鼠光癌模型具有保护作用。在这项研究中，我们表明，局部应用(-)-表没食子儿茶素没食子酸酯(EGCG)，绿茶的主要多酚成分(3毫克/只)，在单一的低剂量UVB照射(72MJ/cm(2))之前，防止了UVB诱导的接触超敏反应的抑制和对接触敏化剂2，4-二硝基氟苯的耐受，在UVB暴露前局部应用EGCG减少了CD11b+单核细胞/巨噬细胞和中性粒细胞渗入皮肤炎症损伤的数量，这被认为是造成紫外线诱导的免疫抑制状态的原因。此外，在UVB暴露前应用EGCG可减少UVB诱导的免疫调节细胞因子IL-10在皮肤和引流淋巴结(DLN)中的产生，而被认为是诱导接触敏感性的介质和佐剂的IL-12的产生与UVB单独暴露小鼠相比显著增加。综上所述，我们的研究结果表明，EGCG通过以下途径对UVB诱导的免疫抑制和耐受诱导产生保护作用：(1)阻断UVB诱导的CD11b+细胞向皮肤的渗透；(2)减少皮肤和DLN中IL-10的产生；(3)显著增加DLN中IL-12的产生，EGCG对UVB诱导的免疫抑制的保护作用可能与其对抗UVB诱导的光癌作用有关。
UV exposure of the skin, particularly UVB (290-320 nm), causes adverse biological effects, including alterations in cutaneous immune cells, photoaging and photocarcinogenesis. Several studies have shown that polyphenolic compounds isolated from green tea afford protection against UVB-induced inflammatory responses and photocarcinogenesis in murine models. In this study we show that topical application of (-)-epigallocatechin-3-gallate (EGCG) (3 mg/mouse), a major polyphenolic component of green tea, before a single low dose UVB exposure (72 mJ/cm(2)) to C3H/HeN mice prevented UVB-induced inhibition of the contact hypersensitivity response and tolerance induction to the contact sensitizer 2,4-dinitrofluorobenzene, Topical application of EGCG before UVB exposure reduced the number of CD11b+ monocytes/macrophages and neutrophils infiltrating into skin inflammatory lesions, which are considered to be responsible for creating the UV-induced immunosuppressive state. In addition, application of EGCG before UVB exposure decreased UVB-induced production of the immunomodulatory cytokine interleukin (IL)-10 in skin as well as in draining lymph nodes (DLN), whereas production of IL-12, which is considered to be a mediator and adjuvant for induction of contact sensitivity, was found to be markedly increased in DLN when compared with UVB alone-exposed mice. Taken together, our data demonstrate that EGCG protects against UVB-induced immunosuppression and tolerance induction by: (i) blocking UVB-induced infiltration of CD11b+ cells into the skin; (ii) reducing IL-10 production in skin as well as in DLN; (iii) markedly increasing IL-12 production in DLN, Protection against UVB-induced immunosuppression by EGCG may be associated with protection against UVB-induced photocarcinogenesis.