Molecular Mechanisms of UV-Induced Apoptosis and Its Effects on Skin Residential Cells: The Implication in UV-Based Phototherapy.
Molecular Mechanisms of UV-Induced Apoptosis and Its Effects on Skin Residential Cells: The Implication in UV-Based Phototherapy.
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DOI：
10.3390/ijms14036414
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发表时间：
2013-03-20
影响因子：
5.6
通讯作者：
Wei YH
中科院分区：
文献类型：
--
作者：
Lee CH;Wu SB;Hong CH;Yu HS;Wei YH
人体皮肤是一个完整的系统，作为一个物理和免疫屏障，以抵御外界病原体，有毒物质和有害辐射。在全球变暖的背景下，来自太阳的环境紫外线（UV）可能在调节几种重要的生物反应方面发挥更积极的作用。UV射线首先遇到最上面的表皮角质形成细胞，引起细胞凋亡。紫外线诱导角质形成细胞凋亡的分子机制包括直接DNA损伤（内在）、细胞表面死亡受体聚集（外在）和ROS的产生。当凋亡的角质形成细胞被邻近的未成熟朗格汉斯细胞（LC）处理时，不适当地激活的朗格汉斯细胞可导致免疫抑制。此外，紫外线可耗尽表皮中的LC并损害其迁移能力，导致其在真皮中积累。有趣的是，NF-κB受体激活剂（RANK）通过UV激活LC可以诱导由于Bcl-xL上调而引起的促存活和抗凋亡信号，从而导致调节性T细胞的产生。同时，生理剂量的紫外线也可以促进黑素细胞的存活和黑素合成。与其在角质形成细胞中的作用类似，治疗剂量的UV可以诱导细胞周期停滞，激活抗氧化剂和DNA修复酶，并通过黑素细胞中Bcl-2家族蛋白的易位诱导细胞凋亡，以确保黑素细胞的基因组完整性和存活。此外，紫外线可以引发维生素D的合成，维生素D是有助于DNA修复和免疫调节的各种类型皮肤细胞的钙稳态的重要分子。综上所述，紫外线对细胞凋亡的上述影响及其相关的生物学效应，如对皮肤驻留细胞的增殖抑制、黑色素合成和免疫调节，为光疗提供了完整的生物化学和分子生物学基础，光疗已被广泛用于治疗许多皮肤病。
The human skin is an integral system that acts as a physical and immunological barrier to outside pathogens, toxicants, and harmful irradiations. Environmental ultraviolet rays (UV) from the sun might potentially play a more active role in regulating several important biological responses in the context of global warming. UV rays first encounter the uppermost epidermal keratinocytes causing apoptosis. The molecular mechanisms of UV-induced apoptosis of keratinocytes include direct DNA damage (intrinsic), clustering of death receptors on the cell surface (extrinsic), and generation of ROS. When apoptotic keratinocytes are processed by adjacent immature Langerhans cells (LCs), the inappropriately activated Langerhans cells could result in immunosuppression. Furthermore, UV can deplete LCs in the epidermis and impair their migratory capacity, leading to their accumulation in the dermis. Intriguingly, receptor activator of NF-κB (RANK) activation of LCs by UV can induce the pro-survival and anti-apoptotic signals due to the upregulation of Bcl-xL, leading to the generation of regulatory T cells. Meanwhile, a physiological dosage of UV can also enhance melanocyte survival and melanogenesis. Analogous to its effect in keratinocytes, a therapeutic dosage of UV can induce cell cycle arrest, activate antioxidant and DNA repair enzymes, and induce apoptosis through translocation of the Bcl-2 family proteins in melanocytes to ensure genomic integrity and survival of melanocytes. Furthermore, UV can elicit the synthesis of vitamin D, an important molecule in calcium homeostasis of various types of skin cells contributing to DNA repair and immunomodulation. Taken together, the above-mentioned effects of UV on apoptosis and its related biological effects such as proliferation inhibition, melanin synthesis, and immunomodulations on skin residential cells have provided an integrated biochemical and molecular biological basis for phototherapy that has been widely used in the treatment of many dermatological diseases.
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DOI：
10.1084/jem.158.3.781
发表时间：
1983-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Elmets CA;Bergstresser PR;Tigelaar RE;Wood PJ;Streilein JW
通讯作者：
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影响因子：
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影响因子：
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Ollinger, Karin M.
影响因子：
6.5
作者：
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作者：
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