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.
Highlights
The skin is the largest organ in the human body [1]
ultraviolet rays (UV) radiation can cause damage to the molecular targets located in the cytosol and cell membranes of keratinocytes
UV may result in the depletion of epidermal Langerhans cells (LCs) and dermal T lymphocytes, which lead to Treg activation in the lymph nodes
Summary
The skin covers the whole body surface and acts as a dynamic barrier to prevent water evaporation from the human body. It prevents the entrance of noxious substances and pathogens into vital internal organs [2]. A network composed of delicate physical, chemical, and immunological barriers in the skin makes it a perfect organ to protect the integrity of the human body [3]. In this review we discuss the effect of UVR on human skin with a focus on physiological and pathological apoptosis. We review the application of UVR-based phototherapy in medical care focusing on apoptosis and its related biological effects in different skin residential cells
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