PYRIMIDINE DIMERS IN DNA INITIATE SYSTEMIC IMMUNOSUPPRESSION IN UV-IRRADIATED MICE
PYRIMIDINE DIMERS IN DNA INITIATE SYSTEMIC IMMUNOSUPPRESSION IN UV-IRRADIATED MICE
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DOI：
10.1073/pnas.89.16.7516
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发表时间：
1992-08-15
影响因子：
11.1
通讯作者：
YAROSH, DB
中科院分区：
文献类型：
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作者：
KRIPKE, ML;COX, PA;YAROSH, DB
将小鼠皮肤暴露在紫外线辐射下会干扰在非辐射部位启动的延迟和接触性超敏免疫反应的诱导。紫外线辐射的这些免疫抑制作用的分子靶标在皮肤中的特性仍然存在争议。为了验证DNA是紫外线诱导的全身免疫抑制的目标这一假设，我们将C3H小鼠暴露在紫外线辐射下，然后使用脂质体将二聚体特异性切除修复酶原位输送到表皮。脂质体包裹的T4核酸内切酶V应用于紫外线照射的小鼠皮肤，减少了表皮中环丁烷嘧啶二聚体的数量，并防止了延迟性和接触性超敏反应的抑制。此外，抑制性淋巴样细胞的形成受到抑制。对照组，脂质体包埋的热灭活核酸内切酶无作用。这些研究表明，DNA是紫外线辐射产生全身免疫抑制的主要靶点，并表明紫外线辐射介导这些类型的免疫抑制的主要分子事件是嘧啶二聚体的形成。此外，他们还表明，紫外线照射后将病变特异的DNA修复酶输送到活的皮肤是恢复免疫功能的有效工具，并表明这种方法可能广泛适用于防止DNA损伤引起的其他变化。
Exposing the skin of mice to UV radiation interferes with the induction of delayed and contact hypersensitivity immune responses initiated at nonirradiated sites. The identity of the molecular target in the skin for these immunosuppressive effects of UV radiation remains controversial. To test the hypothesis that DNA is the target for UV-induced systemic immunosuppression, we exposed C3H mice to UV radiation and then used liposomes to deliver a dimer-specific excision repair enzyme into the epidermis in situ. The application of T4 endonuclease V encapsulated in liposomes to UV-irradiated mouse skin decreased the number of cyclobutane pyrimidine dimers in the epidermis and prevented suppression of both delayed and contact hypersensitivity responses. Moreover, the formation of suppressor lymphoid cells was inhibited. Control, heat-inactivated endonuclease encapsulated in liposomes had no effect. These studies demonstrate that DNA is the major target of UV radiation in the generation of systemic immunosuppression and suggest that the primary molecular event mediating these types of immunosuppression by UV radiation is the formation of pyrimidine dimers. Furthermore, they illustrate that the delivery of lesion-specific DNA repair enzymes to living skin after UV irradiation is an effective tool for restoring immune function and suggest that this approach may be broadly applicable to preventing other alterations caused by DNA damage.