The relationship between DNA damage and immunosuppression by ultraviolet radiation

紫外线损伤DNA与免疫抑制的关系

基本信息

批准号：
09670901
负责人：
HORIO Takeshi
金额：
$ 1.86万
依托单位：
Kansai Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

The skin is an important immune organ which is composed of various immune competent cells. linmunologic functions of the skin are impaired by ultraviolet radiation(UVR), since the skin is an outermost organ.First, we investigated the effect of mid-wave uv(UVR) on the induction of contact hypersensitivity. A variety of factors including total dose of UVR, devided UVR exposure, hapten concentration, and application area, modulated local and systemic UVR-induced inmiunosuppression.The carcinogenesis of UVR has been well known. Gene-mutations based on the DNA-damage had been belived to be a main action of UVR in the carcinogenesis. Therefore, skin cancers easily develop in patients with xeroderma pigmentosum(XP) who have a defect in repair of DNA damage. Recently, however, it has been elucidated that UVR-induced suppression of tumor immunity is also involved. We demonstrated that XP modelambda mice, which were established by gene-targetting, easily develop not only skin cancers but also acute inflanunation and immunosuppression by UVR.This suggests that there may be close relationships among DNA-damage, UV-inflammation and immunosuppression. Furtheremore, UVR greatly suppressed the activity of natural killer cells. Most recently we found that XP mouse skin can produce a great amount of prostaglandins after irradiation of U-yR.We are now investigating if excess amounts of prostaglandins can explain the enhanced inflammation, immunosuppression and impaired NK cell activity.

皮肤是由各种免疫竞争细胞组成的重要免疫器官。皮肤的linmunologic功能受到紫外线辐射（UVR）的损害，因为皮肤是最外层的器官。首先，我们研究了中波紫外线（UVR）对诱导接触性超敏性的影响。多种因素包括UVR的总剂量，无uvr暴露，触发浓度和应用区域，调节局部和全身性UVR诱导的不抑制作用。UVR的致癌作用众所周知。基于DNA破坏的基因杂种已被认为是癌发生中UVR的主要作用。因此，皮肤癌很容易发育在静脉皮色素（XP）的患者中，他们的DNA损伤修复缺陷。然而，最近，已经阐明了UVR诱导的肿瘤免疫抑制。我们证明，通过靶向基因靶向建立的XP ModelAmbda小鼠不仅可以很容易地发展出皮肤癌，而且还可以通过UVR进行急性膨胀和免疫抑制。这表明DNA损伤，UV-炎症和免疫抑制之间可能存在密切的关系。逐渐地，UVR极大地抑制了天然杀伤细胞的活性。最近，我们发现XP小鼠皮肤在U-yr辐照后可以产生大量的前列腺素。我们现在正在研究是否有过多的前列腺素可以解释增强的炎症，免疫抑制和NK细胞活性受损。