p53 and Fas ligand are required for psoralen and UVA-induced apoptosis in mouse epidermal cells.
p53 and Fas ligand are required for psoralen and UVA-induced apoptosis in mouse epidermal cells.
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p53 和 Fas 配体是补骨脂素和 UVA 诱导的小鼠表皮细胞凋亡所必需的。
DOI：
10.1038/sj.cdd.4401007
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发表时间：
2002
影响因子：
12.4
通讯作者：
Ananthaswamy,HN
中科院分区：
文献类型：
--
作者：
Santamaria,AB;Davis,DW;Nghiem,DX;McConkey,DJ;Ullrich,SE;Kapoor,M;Lozano,G;Ananthaswamy,HN
8-甲氧基补骨脂素（8-MOP）和紫外线-A（UVA）辐射（320-400 nm）（PUVA）的组合广泛用于治疗银屑病和其它皮肤病。PUVA在消除表皮中的过度增殖细胞方面非常有效，但其作用机制尚未完全阐明。在这项研究中，我们使用永生化的JB 6小鼠表皮细胞，p53−/−和Fas配体缺陷（gld）小鼠来研究PUVA诱导细胞死亡的分子机制。结果表明PUVA处理诱导JB 6细胞凋亡。此外，PUVA处理JB 6细胞导致p53稳定化、磷酸化和核定位以及诱导p21 Waf/Cip 1和caspase-3活性。体内研究表明，与p53 +/+小鼠相比，PUVA治疗在p53−/−小鼠的表皮中诱导的细胞凋亡显著较少。此外，与野生型小鼠相比，FasL缺陷型（gld）小鼠对PUVA诱导的细胞凋亡具有完全抗性。这些结果表明，PUVA治疗诱导小鼠表皮细胞在体外和体内的细胞凋亡和p53和Fas/Fas配体的相互作用，需要这个过程中，至少在体内。这意味着类似的机制可能涉及消除银屑病角质形成细胞从人类皮肤后PUVA治疗。
A combination of 8-methoxypsoralen (8-MOP) and ultraviolet-A (UVA) radiation (320–400 nm)(PUVA) is widely used in the treatment of psoriasis and other skin diseases. PUVA is highly effective in eliminating hyperproliferative cells in the epidermis, but its mechanism of action has not been fully elucidated. In this study, we used immortalized JB6 mouse epidermal cells, p53−/−, and Fas ligand deficient (gld) mice to investigate the molecular mechanism by which PUVA induces cell death. The results indicate that PUVA treatment induces apoptosis in JB6 cells. In addition, PUVA treatment of JB6 cells results in p53 stabilization, phosphorylation, and nuclear localization as well as induction of p21 Waf/Cip1 and caspase-3 activity. In vivo studies reveal that PUVA treatment induces significantly less apoptosis in the epidermis of p53−/− mice compared to p53+/+ mice. Furthermore, FasL-deficient (gld) mice are completely resistant to PUVA-induced apoptosis compared to wild-type mice. These results indicate that PUVA treatment induces apoptosis in mouse epidermal cells in vitro and in vivo and that p53 and Fas/Fas ligand interactions are required for this process, at least in vivo. This implies that similar mechanisms may be involved in the elimination of psoriatic keratinocytes from human skin following PUVA therapy.