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      Molecular Mechanisms of UV-Induced Apoptosis and Its Effects on Skin Residential Cells: The Implication in UV-Based Phototherapy

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          Abstract

          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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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                Molecular Diversity Preservation International (MDPI)
                1422-0067
                March 2013
                20 March 2013
                : 14
                : 3
                : 6414-6435
                Affiliations
                [1 ]Department of Dermatology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan; E-Mail: dermlee@ 123456gmail.com
                [2 ]Department of Dermatology, Kaohsiung Medical University, Kaohsiung 807, Taiwan; E-Mail: dermyu@ 123456kmu.edu.tw
                [3 ]Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
                [4 ]Department of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan; E-Mail: labboy700110@ 123456gmail.com
                [5 ]Department of Dermatology, National Yang-Ming University, Taipei 112, Taiwan; E-Mail: zieben@ 123456gmail.com
                [6 ]Department of Dermatology, Kaohsiung Veterans General Hospital, Kaohsiung City 813, Taiwan
                [7 ]Department of Medicine, Mackay Medical College, New Taipei City 252, Taiwan
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: joeman@ 123456ym.edu.tw ; Tel.: +886-2-2826-7118; Fax: +886-2-2826-4843.
                Article
                ijms-14-06414
                10.3390/ijms14036414
                3634415
                23519108
                © 2013 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

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