Moloney S J, Learn D B
Department of Skin Biology Research, Schering-Plough HealthCare Products Inc., Memphis, TN 38151.
Photochem Photobiol. 1992 Oct;56(4):495-504. doi: 10.1111/j.1751-1097.1992.tb02193.x.
The mechanisms that cause skin wrinkling in response to chronic exposure to sunlight are unknown. We investigated the possibility that wrinkling of Skh-1 hairless mice is associated with an ultraviolet (UV) radiation-induced immunologic alteration. Exposing Skh-1 hairless mice to a regimen of nonerythemal UV-B (290-320 nm) radiation induced skin wrinkles after 6-7 weeks. Concomitant treatment with cyclosporin A decreased the time to the onset of wrinkles to approximately 4 weeks. Exposing HRS/J hairless mice or athymic nude mice to a similar nonerythemal UV-B radiation regimen for 10 weeks failed to induce skin wrinkles. Concomitant administration of cyclosporin A and UV-B radiation for 7 weeks to HRS/J hairless mice induced no skin wrinkles. Ultraviolet-B or UV-B plus cyclosporin A exposure caused increased immunohistochemical staining for Ia and F4/80 antigens in the upper dermis of tissue from Skh-1 mice, as compared to controls. Treating Skh-1 mice with UV-B radiation plus cyclosporin A was also associated with a large increase in the number of CD3+ cells in the dermis. These staining patterns were absent in similarly treated HRS/J hairless mice. Dermal mast cell numbers in Skh-1 mice were 2-3-fold higher than in HRS/J, athymic nude or NSA mice. Treatment with cyclosporin A increased Skh-1 dermal mast cell numbers approximately 2-fold but had no effect on the dermal mast cell numbers in HRS/J or NSA mice. Based on these findings we postulate that UV-B light and cyclosporin A exacerbate an immunological condition in Skh-1 mice, one consequence of which is manifested as skin wrinkles. Thus, the induction of skin wrinkles in this mouse strain may have no relevance to the wrinkles observed in human skin after chronic exposure to sunlight.
长期暴露于阳光下导致皮肤起皱的机制尚不清楚。我们研究了Skh-1无毛小鼠皮肤起皱是否与紫外线（UV）辐射诱导的免疫改变有关。将Skh-1无毛小鼠暴露于非红斑性UV-B（290 - 320 nm）辐射方案下，6 - 7周后会诱导皮肤出现皱纹。同时给予环孢素A可将皱纹出现的时间缩短至约4周。将HRS/J无毛小鼠或无胸腺裸鼠暴露于类似的非红斑性UV-B辐射方案10周未能诱导皮肤皱纹。同时给予环孢素A和UV-B辐射7周，HRS/J无毛小鼠未出现皮肤皱纹。与对照组相比，UV-B或UV-B加环孢素A暴露导致Skh-1小鼠组织真皮上层Ia和F4/80抗原的免疫组化染色增加。用UV-B辐射加环孢素A处理Skh-1小鼠还与真皮中CD3 +细胞数量的大幅增加有关。在同样处理的HRS/J无毛小鼠中未出现这些染色模式。Skh-1小鼠的真皮肥大细胞数量比HRS/J、无胸腺裸鼠或NSA小鼠高2 - 3倍。用环孢素A处理使Skh-1真皮肥大细胞数量增加约2倍，但对HRS/J或NSA小鼠的真皮肥大细胞数量没有影响。基于这些发现，我们推测UV-B光和环孢素A会加剧Skh-1小鼠的免疫状况，其后果之一表现为皮肤皱纹。因此，该小鼠品系中皮肤皱纹的诱导可能与人类长期暴露于阳光下后观察到的皱纹无关。
