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首页> 外文期刊>The Journal of investigative dermatology. >Vitamin D enhances ALA-induced protoporphyrin IX production and photodynamic cell death in 3-D organotypic cultures of keratinocytes.
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Vitamin D enhances ALA-induced protoporphyrin IX production and photodynamic cell death in 3-D organotypic cultures of keratinocytes.

机译：在角质形成细胞的3-D有机型培养物中，维生素D增强了ALA诱导的原卟啉IX的产生和光动力细胞死亡。

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摘要

Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is based upon the intracellular synthesis of protoporphyrin IX (PpIX), which absorbs light and targets metabolically active cells. We tested the hypothesis that levels of PpIX within keratinocytes might be increased by vitamin D (Vit D), a differentiation-promoting hormone. Vit D promoted terminal differentiation in monolayer cultures of rat epidermal keratinocytes (REKs), but high PpIX signals were found only in stratifying islands. To simulate a normal epidermis, REKs were grown in organotypic cultures. The presence of Vit D (10(-10) M for 4 days) led to heightened expression of terminal differentiation markers (stratum corneum, K10, and loricrin). PpIX levels, at 4 hours after addition of ALA (1 mM), were significantly increased in the Vit D-preconditioned cultures by confocal fluorescence microscopy and semiquantitative image analysis. Maximal PpIX induction was seen at (Vit D) 10(-12)-10(-10) M. Phototoxic cell killing after exposure to 635 nm light was significantly higher in Vit D-preconditioned cultures. No differences in apoptotic markers between Vit D and control cultures were seen, suggesting that Vit D augments photodynamic cell death via alternative pathways (e.g., necrosis). In summary, Vit D may be useful as a biological enhancer of ALA-based PDT.
机译：5-氨基乙酰丙酸（ALA）的光动力疗法（PDT）基于原卟啉IX（PpIX）的细胞内合成，它吸收光并靶向代谢活性细胞。我们测试了一种假设，即角质形成细胞中PpIX的水平可能会被维生素D（Vit D）（一种促进分化的激素）增加。 Vit D促进大鼠表皮角质形成细胞（REKs）的单层培养中的终末分化，但仅在分层岛中发现了高PpIX信号。为了模拟正常的表皮，REK在器官型培养物中生长。 Vit D（10（-10）M持续4天）的存在导致末端分化标记物（角质层，K10和loricrin）的表达增加。通过共聚焦荧光显微镜和半定量图像分析，在添加Vit D预处理的培养物中，添加ALA（1 mM）后4小时的PpIX水平显着增加。在（Vit D）10（-12）-10（-10）M处观察到最大的PpIX诱导。在Vit D预处理的培养物中，暴露于635 nm光后杀死光毒性细胞明显更高。在Vit D和对照培养物之间未见凋亡标记物的差异，表明Vit D通过替代途径（例如坏死）增加了光动力细胞的死亡。总之，Vit D可用作基于ALA的PDT的生物增强剂。

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