The relationship between DNA damage and immunosuppression by ultraviolet radiation

紫外线损伤DNA与免疫抑制的关系

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670901/
• 关键词: Ultraviolet light; DNA damage; Immunosuppression; Xeroderma pigmentosum; NK cell; 光免疫学; DNA障害; ランゲルハンス細胞; 接触アレルギー

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.

皮肤是重要的免疫器官，由多种免疫活性细胞组成。由于皮肤是最外层的器官，因此皮肤的免疫功能会受到紫外线辐射（UVR）的损害。首先，我们研究了中波紫外线（UVR）对诱发接触性超敏反应的影响。多种因素包括UVR总剂量、UVR暴露量、半抗原浓度和应用区域等，调节局部和全身UVR诱导的免疫抑制。UVR的致癌作用已众所周知。基于 DNA 损伤的基因突变被认为是 UVR 在致癌作用中的主要作用。因此，DNA损伤修复缺陷的着色性干皮病（XP）患者很容易患上皮肤癌。然而，最近已经阐明，UVR 诱导的肿瘤免疫抑制也参与其中。我们证明，通过基因靶向建立的 XP modelambda 小鼠不仅容易患皮肤癌，而且容易患上紫外线引起的急性炎症和免疫抑制。这表明 DNA 损伤、紫外线炎症和免疫抑制之间可能存在密切关系。此外，紫外线极大地抑制了自然杀伤细胞的活性。最近我们发现XP小鼠皮肤在U-yR照射后可以产生大量的前列腺素。我们现在正在研究过量的前列腺素是否可以解释炎症增强、免疫抑制和NK细胞活性受损的原因。

项目成果

Miyauchi H et al: "Ultraviolet B-Induced local immunosuppression of contact hypersensitivity is modulated by ultraviolet irradiation and hapten application" J Invest Dermatol. 104. 364-369 (1995)

Miyauchi H 等人：“紫外线 B 诱导的接触性超敏反应的局部免疫抑制是通过紫外线照射和半抗原应用来调节的”J Invest Dermatol。

Miyauchi H et al: "Ultraviolet B-induced local immunosupp-ression of contact hypersensitivity is modulated by ultravi-olet irradiation and hapten application" J.Invest Dermatol. 104. 364-369 (1995)

Miyauchi H 等人：“紫外线 B 诱导的接触性超敏反应的局部免疫抑制是通过紫外线照射和半抗原应用来调节的”J.Invest Dermatol。

Nakane H et al: "High Incidence of ultraviolet-B-or chemical-carcinogen-induced skin tumors in mice lacking the xeroderma pigmentosum group A gene" Nature. 37 : 6545. 165-168 (1995)

Nakane H 等人：“缺乏色素性干皮病 A 组基因的小鼠中，紫外线 B 族或化学致癌物诱发的皮肤肿瘤发生率很高”《自然》杂志。

Miyauchi-Hashimoto H et al: "Suppressive effect of UVB radiation on contact sensitization In mice II.Systemic immunosuppression is modulated by UV radiation and hapten application" Photodermatol Photoimmunol Photomed. 12. 137-144 (1996)

Miyauchi-Hashimoto H 等人：“UVB 辐射对小鼠接触致敏的抑制作用 II。系统性免疫抑制通过紫外线辐射和半抗原应用进行调节”Photodermatol Photoimmunol Photomed。

Miyauchi-Hashimoto H et al: "Enhanced inflammation and i-mmunosuppression by ultraviolet radiation in xeroderma p-igmentosum group A (XPA) model mice" JInvest Dermatol. 107. 343-348 (1996)

Miyauchi-Hashimoto H 等人：“紫外线辐射增强 A 组干皮病 (XPA) 模型小鼠的炎症和免疫抑制”JInvest Dermatol。