UVB-induced alterations in permeability barrier function: Roles for epidermal hyperproliferation and thymocyte-mediated response
UVB-induced alterations in permeability barrier function: Roles for epidermal hyperproliferation and thymocyte-mediated response
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DOI：
10.1111/1523-1747.ep12292163
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发表时间：
1997-05-01
影响因子：
6.5
通讯作者：
Holleran, WM
中科院分区：
文献类型：
--
作者：
Haratake, A;Uchida, Y;Holleran, WM
紫外线照射会引起多种皮肤反应，包括表皮渗透性屏障功能的破坏，其基础尚不清楚。在此，我们研究了过度增殖和炎症在 UVB 诱导的屏障破坏发病机制中的各自作用，成年无毛小鼠暴露于剂量不断增加的 UVB（1.5-7.5 MED），每天监测经表皮水分流失（TEWL）长达 7 天，TEWL 增加的程度取决于UVB 剂量，但对于所有剂量，增加在大于或等于 48 小时后开始，并在 96 小时达到峰值，减少 120 小时，表皮 [H-3] 胸苷掺入在 24 小时增加，并在 48 小时达到峰值 (570%)，先于 TEWL 的最大增加。环孢素 A、甲氨蝶呤、5-氟尿嘧啶或阿拉伯糖基胞嘧啶显着减少了 UVB 诱导的 TEWL 增加，无胸腺裸鼠也表现出对 UVB 的反应明显减弱，并且 DNA 合成在 48 小时时没有增加。移植富含 T 细胞的混合免疫细胞的无胸腺小鼠显着恢复了对 UVB 诱导的过度增殖和屏障缺陷的敏感性，最后，尽管 UVB 暴露增加整个皮肤样本中的 PGE 水平（1-3 小时内 2 至 3 倍；p < 0.005），这种增加被局部吲哚美辛完全阻断，并且局部吲哚美辛和局部糖皮质激素都不能阻断屏障异常的发展。这些结果表明，(i) UVB 会延迟屏障功能的改变，并且 (ii) 表皮增殖反应和胸腺细胞介导的事件（但不是 PGE(2) 的产生和非特异性炎症）似乎有助于 UVB 诱导的渗透性屏障的废除。
UV irradiation induces a variety of cutaneous responses, including disruption of epidermal permeability barrier function, the basis for which is not known, Herein, we investigated the separate roles of hyperproliferation and inflammation in the pathogenesis of UVB-induced barrier disruption, Adult hairless mice were exposed to increasing doses of UVB (1.5-7.5 MED), and transepidermal water loss (TEWL) was monitored daily for up to 7 d, The extent of TEWL increase was dependent on the UVB dose, but with all doses, the increase began after greater than or equal to 48 h and peaked at 96 h, decreasing by 120 h, Epidermal [H-3]thymidine incorporation increased at 24 h and peaked at 48 h (570%), preceding the maximal increase in TEWL. Cyclosporin A, methotrexate, 5-fluorouracil, or arabinosylcytosine significantly diminished the UVB-induced TEWL increase, Athymic nude mice also displayed a markedly diminished response to UVB, and DNA synthesis did not increased at 48 h, Transplantation of athymic mice with T-cell-enriched mixed immune cells significantly restored sensitivity to both the UVB-induced hyperproliferation and the barrier defect, Finally, although UVB exposure increased PGE, levels in whole skin samples (2- to 3-fold within 1-3 h; p < 0.005), this increase was completely blocked by topical indomethacin, and neither topical indomethacin nor topical glucocorticoids blocked development of the barrier abnormality. These results show that (i) UVB produces delayed alteration in barrier function and (ii) both an epidermal proliferative response and thymocyte-mediated events (but not PGE(2) production and nonspecific inflammation) appear to contribute to UVB-induced abrogation of the permeability barrier.