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Cited by 271Skin Protection and AgingCell death mechanisms and regulationmelanin and skin pigmentation

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

Open access
Lee, Chih-Hung, Wu, Shi-Bei, Hong, Chien-Hui, Yu, Hsin-Su, Wei, Yau-Huei·2013·International Journal of Molecular Sciences
DOI 10.3390/ijms14036414PMC PMC3634415
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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.

AI snapshot

Written from the paper’s full text.

TL;DR

This review synthesizes molecular mechanisms by which UV radiation induces apoptosis in skin residential cells—keratinocytes, Langerhans cells, and melanocytes—and links these effects to immunomodulation, melanogenesis, vitamin D synthesis, and UV-based phototherapy. It argues that UV-induced apoptosis and related cellular responses provide an integrated biochemical basis for treating inflammatory, sclerosing, and neoplastic skin diseases.

Key findings

  • UV-induced keratinocyte apoptosis involves direct DNA photoproducts (CPDs and 6–4PPs), death receptor clustering (CD95/Fas, TNFR, TRAIL receptors), and mitochondrial/intrinsic pathways involving Bcl-2 family proteins and cytochrome c; p53 regulates DNA repair, but basal keratinocyte apoptosis can be p53-independent.
  • UV modulates cutaneous immunity: apoptotic keratinocytes activate immature Langerhans cells; UV depletes epidermal LCs and impairs migration, while RANK/RANKL activation upregulates Bcl-xL and promotes regulatory T cells; UVB decreases IL-12 and IFN-γ-producing T cells by over 50% and increases IL-4 by over 80% during treatment of psoriasis patients.
  • In melanocytes, UV induces paracrine factors (ACTH, endothelin-1, β-FGF, α-MSH), nucleotide excision repair, antioxidant and DNA repair enzymes, cell cycle arrest, and apoptosis via Bcl-2 family translocation; UVA is generally stronger than UVB for pigmentation, and increasing cumulative UV dose above a threshold does not significantly increase pigmentation.
  • UVB synthesizes vitamin D; VDR knockout mice show lower thymine-dimer repair and UV-induced epidermal apoptosis and attenuated epidermal thickening; phototherapy modalities include broadband UVB 290–320 nm, narrowband UVB 311–313 nm, 308-nm excimer laser, UVA1 340–400 nm, PUVA, and photopheresis.

Methods

  • Narrative review; no primary experiments, systematic search, or meta-analysis are described.
  • Synthesizes mechanistic and clinical literature on UVR (100–400 nm; UVA 315–400 nm, UVB 280–315 nm, UVC 100–280 nm) and skin cells including keratinocytes, melanocytes, Langerhans cells, T cells, mast cells, and endothelial cells.
  • Main analysis is qualitative integration of cited studies and a table of phototherapy techniques; no sample size or statistical analysis is reported.

Limitations

  • The paper states no explicit limitations.
  • Evident from the text: it is a narrative review without systematic search or quality assessment, so conclusions rely on cited primary studies and may be subject to selection bias.
  • Evident from the text: clinical implications are largely mechanistic or observational, with no new patient data or formal efficacy comparison presented.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/ijms14036414

Cites

134 of 134 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

53 of 143 cited sources checked · 19 supported · 2 flagged · accuracy not yet measured

  • Premisecitation

    Langerhans cells, after escaping from UV-induced apoptosis, have a decreased capacity to prime naive CD8+ T cells, inducing immunological tolerance.

    “In addition, LCs, after escaping from UV-induced apoptosis, have a decreased capacity to prime naive CD8+ T cells, inducing immunological tolerance [70].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [70] Dudda, 2004, UVB-irradiated dendritic cells fail to tolerize murine CD8 naive or effector T cells, J. Invest. Dermatol source

      The Abstract and Discussion report reduced priming of naïve CD8+ T cells by UVB-irradiated bone marrow-derived dendritic cells, not specifically Langerhans cells. Crucially, the Discussion says those cells do not induce direct tolerance in naïve or effector CD8+ T cells—the opposite of the cited claim's tolerance conclusion. The cited passages also do not establish that the cells had escaped UV-induced apoptosis. (LLM, conf=0.91)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation

    RANK activation of Langerhans cells by UV can induce pro-survival and anti-apoptotic signals due to upregulation of Bcl-xL, leading to generation of regulatory T cells.

    “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.”
    Quote in the paperSubstantial claim2 of 4 sources checked
    • cites [65] Loser, 2006, Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells, Nat. Med source
    • cites [67] Chen, 2004, TRANCE counteracts FasL-mediated apoptosis of murine bone marrow-derived dendritic cells, Cell Immunol source
    • cites [68] Cremer, 2002, Long-lived immature dendritic cells mediated by TRANCE-RANK interaction, Blood source

      The section on rescuing Langerhans-type dendritic cells from cell death reports that TRANCE–RANK engagement supports their viability and is associated with Bcl-2 expression (page unavailable). The paper does not report UV-induced RANK activation, Bcl-xL upregulation, or regulatory T-cell generation by those cells. Its Introduction mentions regulatory T cells only in connection with a mouse diabetes model. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [69] Josien, 2000, TRANCE, a tumor necrosis factor family member, enhances the longevity and adjuvant properties of dendritic cells in vivo, J. Exp. Med source

      The Introduction (page unavailable) says TRANCE promotes survival of mature dendritic cells, most likely by upregulating Bcl-XL. The paper does not establish that UV activates RANK in Langerhans cells or that this pathway generates regulatory T cells; it instead examines TRANCE-treated dendritic cells and antigen-specific T-cell responses. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Premisecitation

    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.

    “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.”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [81] MacLaughlin, 1982, Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin, Science source
    • cites [85] Ellison, 2008, Inactivation of the vitamin D receptor enhances susceptibility of murine skin to UV-induced tumorigenesis, J. Invest. Dermatol source
    • cites [86] Malaguarnera, 2011, Vitamin D3: A helpful immuno-modulator, Immunology source

      The Vitamin D3 synthesis section says UV light initiates vitamin D3 production in skin, and the Introduction describes vitamin D3’s role in calcium homeostasis and immune regulation. However, the copy does not establish calcium homeostasis specifically in various skin-cell types or a contribution to DNA repair; the DNA-related passages concern gene regulation, not repair. No page number is available for these passages. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Premisecitation

    A prototype of UV-induced apoptosis of keratinocytes is the formation of epidermal sunburn cells that are destined to apoptosis after sun exposure.

    “A prototype of UV-induced apoptosis of keratinocytes is the formation of epidermal sunburn cells that are destined to apoptosis after sun exposure [22].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [22] Kulms, 2000, Molecular mechanisms of UV-induced apoptosis, Photodermatol. Photoimmunol. Photomed source
  • Premisecitation

    UVB radiation is considered the main cause of sunburn and skin cancers.

    “Since UVB is only partially blocked by clouds or fog, UVB radiation is considered as the main cause of sunburn and skin cancers [12].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [12] Coelho, 2010, UVA tanning is involved in the increased incidence of skin cancers in fair-skinned young women, Pigment Cell Melanoma Res source

      The Introduction (page unavailable) says UV exposure causes nonmelanoma skin cancers and links it to erythema, or sunburn. The paper does not identify UVB specifically as the main cause of either, and its “UV burden” section discusses a possible role for UVA in melanoma. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Classified as probably not a substantial claim. 16
  • May combine two claims. 54

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The terminal differentiation process in the cornified layer represents the prototype of physiological apoptosis in the human epidermis.

    “Thus, the terminal differentiation process in the cornified layer in this way represents the prototype of physiological apoptosis in the human epidermis [4].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [4] Pincelli, 2010, Keratinocyte stem cells: Friends and foes, J. Cell Physiol source

      In “Stem cells and apoptosis” (page unavailable), the paper says epidermal differentiation and apoptosis are clearly different at the molecular level. It describes terminal differentiation as a normal epidermal process, not as the prototype of physiological apoptosis. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Langerhans cells are professional antigen presenting cells in the epidermis and their long dendritic structures comprise the first line immunological barriers.

    “LCs are professional antigen presenting cells (APCs) in the epidermis of the skin, and their long dendritic structures comprise the first line immunological barriers [6].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [6] Koch, 2006, Skin homing of Langerhans cell precursors: Adhesion, chemotaxis, and migration, J. Allergy Clin. Immunol source

      The Abstract identifies Langerhans cells as epidermal antigen-presenting dendritic cells and calls them a critical immune outpost at the interface with the external environment. The Conclusion likewise describes their role in controlling immune responses. Neither passage says that their dendritic structures are long or that those structures comprise a first-line immunological barrier; page numbers are unavailable in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    UV can deplete Langerhans cells in the epidermis and impair their migratory capacity, leading to their accumulation in the dermis.

    “Furthermore, UV can deplete LCs in the epidermis and impair their migratory capacity, leading to their accumulation in the dermis.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [62] Kolgen, 2002, Epidermal langerhans cell depletion after artificial ultraviolet B irradiation of human skin in vivo: Apoptosis versus migration, J. Invest. Dermatol source

      The Results and Discussion (pp. 812–817) support epidermal Langerhans cell depletion after UVB exposure and identify migration as its main cause. They do not show that UV impairs the cells’ migratory capacity or causes them to accumulate in the dermis; the study instead detected migrating cells in blister fluid. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    T-T lesions may help generate N-Ras mutations in murine squamous cell carcinomas and in human melanomas.

    “It has been reported that T-T lesions may help generate N-Ras mutations in murine squamous cell carcinomas [20] and in human melanomas [21].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [20] Pierceall, 1992, N-ras mutation in ultraviolet radiation-induced murine skin cancers, Cancer Res
    • cites [21] Jiveskog, 1998, N-ras mutations are common in melanomas from sun-exposed skin of humans but rare in mucosal membranes or unexposed skin, J. Invest. Dermatol source

  • May combine two claims.

    Premisecitation

    A physiological dosage of UV can enhance melanocyte survival and melanogenesis.

    “Meanwhile, a physiological dosage of UV can also enhance melanocyte survival and melanogenesis.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [75] Kobayashi, 1998, Supranuclear melanin caps reduce ultraviolet induced DNA photoproducts in human epidermis, J. Invest. Dermatol source

      The Discussion (page not provided) says evidence suggests that UV-induced DNA photoproducts or their repair stimulate melanin synthesis. It does not say that a physiological UV dose enhances melanocyte survival, and its own experiments assessed DNA photoproducts rather than survival or melanogenesis. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    UV rays first encounter the uppermost epidermal keratinocytes and cause apoptosis.

    “UV rays first encounter the uppermost epidermal keratinocytes causing apoptosis.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [22] Kulms, 2000, Molecular mechanisms of UV-induced apoptosis, Photodermatol. Photoimmunol. Photomed source

      The Abstract identifies sunburn cells in UV-exposed skin as keratinocytes undergoing apoptosis after UV irradiation, and the Conclusion likewise discusses UV-induced keratinocyte apoptosis. Our copy does not say that UV rays first encounter the uppermost epidermal keratinocytes or locate the apoptotic cells specifically in that layer. Page numbers are unavailable in the indexed passages. (LLM, conf=0.83)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Both UVB and UVA radiation contribute to freckling, skin wrinkling and the development of skin cancers.

    “In fact, both UVB and UVA radiation contribute to freckling, skin wrinkling and the development of skin cancers [13,14].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [13] Krutmann, 2000, Ultraviolet A radiation-induced biological effects in human skin: Relevance for photoaging and photodermatosis, J. Dermatol. Sci source
    • cites [14] Phan, 2006, Spectral and dose dependence of ultraviolet radiation-induced immunosuppression, Front. Biosci source

      Section 3.4 (Ageing and elastosis; page unavailable) says chronic UVB and UVA exposure contribute to premature skin ageing, supporting the wrinkling component. Section 3.6 (Skin Cancer; page unavailable) supports a role for both wavebands in skin cancer, although it notes uncertainty about their relative roles in human cancers. Section 3.3 discusses pigment darkening, not freckling, so the freckling component is not supported by our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The most biologically active vitamin D metabolite is 1,25-dihydroxyvitamin D3, which is synthesized locally in the skin and systemically after skin exposure to sunlight.

    “The most biologically active vitamin D metabolite is 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], which is synthesized locally in the skin and systemically after skin exposure to sunlight [84].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [84] Hewison, 2010, Vitamin D and the intracrinology of innate immunity, Mol. Cell Endocrinol source

      The Introduction identifies 1,25(OH)2D as the active form of vitamin D and describes its systemic synthesis in the kidney. Section 5 describes localized production in skin keratinocytes under conditions of epidermal wounding. The cited passages do not establish that sunlight exposure triggers either the local or systemic synthesis of 1,25(OH)2D. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    UV radiation and topical 1,25(OH)2D3 can activate dermal mast cells, which are important to determine the extent of UV immunomodulation.

    “For example, UV radiation and topical 1,25(OH)2D3 can also activate dermal mast cells [88,89], which are important to determine the extent of UV immunomodulation [89,90].”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [88] Biggs, 2010, Evidence that vitamin D(3) promotes mast cell-dependent reduction of chronic UVB-induced skin pathology in mice, J. Exp. Med source

      The Results and Discussion (page not provided) suggest that UVB-induced 1α,25(OH)2D3 contributes to dermal mast-cell activation and show that mast cells affect inflammatory cytokines and skin pathology after chronic UVB exposure in mice. The paper does not report topical application of 1,25(OH)2D3 or establish its effect on the extent of UV-induced immunomodulation more generally. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [89] Hart, 1998, Dermal mast cells determine susceptibility to ultraviolet B-induced systemic suppression of contact hypersensitivity responses in mice, J. Exp. Med source

      The paper states that dermal mast cells are activated after UVB irradiation and reports in the Discussion (page not provided) that their prevalence correlates with susceptibility to UVB-induced systemic immunomodulation in mice. It does not address activation by topical 1,25(OH)2D3, and its finding about mast cells concerns systemic rather than local suppression. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [90] Hart, 2002, Mast cells, neuropeptides, histamine, and prostaglandins in UV-induced systemic immunosuppression, Methods source

  • May combine two claims.

    Premisecitation

    UVR can induce the depletion of Langerhans cells in the epidermis and impair the migratory capacity of Langerhans cells, leading to their accumulation in the dermis.

    “UVR can induce the depletion of LCs in the epidermis and impair the migratory capacity of LCs, leading to their accumulation in the dermis [62].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [62] Kolgen, 2002, Epidermal langerhans cell depletion after artificial ultraviolet B irradiation of human skin in vivo: Apoptosis versus migration, J. Invest. Dermatol source

      The Results report epidermal Langerhans-cell depletion after UVB exposure, and the Discussion concludes that the depletion is mainly caused by migration. The paper does not establish that UVB impairs their migratory capacity or causes them to accumulate in the dermis; it detects migrating cells in blister fluid instead. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    UVR isomerizes trans-UCA to cis-UCA, which has potent immunosuppressive properties.

    “UVR isomerizes trans-UCA to cis-UCA, which has potent immunosuppressive properties [58].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [58] Beissert, 2001, IL-12 prevents the inhibitory effects of cis-urocanic acid on tumor antigen presentation by Langerhans cells: Implications for photocarcinogenesis, J. Immunol source

  • May combine two claims.

    Premisecitation

    Langerhans cells derived from mice deficient in the pro-apoptotic Bid gene resist apoptosis and can induce amplified contact hypersensitivity reactions; Bid activation is a critical upstream mediator in UV-induced keratinocyte and LC apoptosis and its absence abrogates UV-induced immune tolerance.

    “In fact, LCs derived from mice deficient in the pro-apoptotic Bid (BH3-interacting death domain protein) gene resist apoptosis and can induce amplified contact hypersensitivity reactions. Bid activation is a critical upstream mediator in UV-induced keratinocyte and LC apoptosis and its absence abrogates UV-induced immune tolerance [74].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [74] Pradhan, 2008, A critical role for the proapoptotic protein bid in ultraviolet-induced immune suppression and cutaneous apoptosis, J. Immunol source

  • May combine two claims.

    Premisecitation

    Activation of Toll-like receptor 1 and TLR2 by tuberculosis enhances 1α-hydroxylase expression, production of antimicrobial peptide cathelicidin, and induction of tolerogenic dendritic cells and T cells.

    “Activation of Toll-like receptor 1 (TLR1) and TLR2 by tuberculosis enhances 1α-hydroxylase expression, the enzyme mediates the synthesis of 1,25(OH)2D3, production of antimicrobial peptide cathelicidin [87], and induction of tolerogenic DCs and T cells [60,84].”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [87] Liu, 2006, Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response, Science source
    • cites [60] Hart, 2011, Modulation of the immune system by UV radiation: More than just the effects of vitamin D?, Nat. Rev. Immunol source
    • cites [84] Hewison, 2010, Vitamin D and the intracrinology of innate immunity, Mol. Cell Endocrinol source

  • May combine two claims.

    Premisecitation

    The cis-UCA induced by UV radiation stimulates the production of reactive oxygen species in keratinocytes, which leads to oxidative DNA damage and downstream immunosuppression.

    “The cis-UCA induced by UV radiation stimulates the production of reactive oxygen species in keratinocytes, which leads to oxidative DNA damage and downstream immunosuppression [59].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [59] Sreevidya, 2010, Agents that reverse UV-Induced immune suppression and photocarcinogenesis affect DNA repair, J. Invest. Dermatol source

      The Results report that cis-UCA induced reactive oxygen species in keratinocytes, and the Discussion reports oxidative DNA damage marked by 8-oxo-dG. The Discussion describes the resulting immune suppression as a suggested pathway, not an established consequence of that damage; the claim states the full causal chain as fact. Page numbers were not available in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Local 1,25(OH)2D3 synthesis activates innate immune responses but suppresses adaptive immune responses.

    “Intriguingly, local 1,25(OH)2D3 synthesis activates innate immune responses, but suppresses adaptive immune responses [86].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [86] Malaguarnera, 2011, Vitamin D3: A helpful immuno-modulator, Immunology source

  • May combine two claims.

    Interpretationcitation

    Oxidative stress and damage elicited by mtDNA mutations lead to mitochondrial dysfunction and increase the susceptibility of affected skin tissue cells to apoptosis upon UV irradiation.

    “Taken together, the results from the other investigators and our laboratory indicate that oxidative stress and damage elicited by mtDNA mutations not only lead to mitochondrial dysfunction but also increase the susceptibility of affected skin tissue cells to apoptosis upon UV irradiation [54–56].”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [54] Liu, 2009, Role of reactive oxygen species-elicited apoptosis in the pathophysiology of mitochondrial and neurodegenerative diseases associated with mitochondrial DNA mutations, J. Formos Med. Assoc source
    • cites [55] Paz, 2008, Mitochondrial dysfunction and cellular stress progression after ultraviolet B irradiation in human keratinocytes, Photodermatol. Photoimmunol. Photomed source
    • cites [56] Schroeder, 2008, Partial depletion of mitochondrial DNA from human skin fibroblasts induces a gene expression profile reminiscent of photoaged skin, J. Invest. Dermatol source

      The Introduction (page unavailable) reports that UVA-induced mtDNA mutations in human dermal fibroblasts were associated with reduced measures of mitochondrial function, and that antioxidants normalized both the mutations and their functional consequences. The Discussion (page unavailable) also reports decreased mitochondrial function after partial mtDNA depletion. Neither passage shows that affected skin cells become more susceptible to apoptosis upon UV irradiation. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    TNFR is clustered and internalized in keratinocytes after UVB irradiation, coupled with recruitment of TRADD and TRAF-2, and there appears to be crosstalk between TNFR and FADD-induced apoptotic pathways.

    “On the other hand, tumor necrosis factor receptor (TNFR) is clustered and internalized in keratinocytes after UVB irradiation. This process is coupled with the recruitment of TNFR1-associated death protein and TNFR-associated factor-2 (TRAF-2) in the human or murine keratinocyte cell lines, respectively. There appears to be crosstalk between TNFR and FADD-induced apoptotic pathways [36].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [36] Tobin, 1998, UVB-induced association of tumor necrosis factor (TNF) receptor 1/TNF receptor-associated factor-2 mediates activation of Rel proteins, Proc. Natl. Acad. Sci. USA source

      The results section reports that UVB irradiation causes TNFR1–TRAF-2 association in murine keratinocytes, with similar results in primary human keratinocytes. The Discussion describes TRADD as an indirect link between TNFR1 and TRAF-2 and proposes a balance between TRADD–FADD apoptotic signaling and TRADD–TRAF-2 protective signaling. Our copy does not report TNFR clustering or internalization, or directly demonstrate UVB-induced TRADD recruitment. Page numbers were not available in the indexed passages. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In T cells, UVB can eliminate the mRNA of IL-12 and decrease interferon-gamma producing T-cells by over 50%.

    “In T cells, UVB can eliminate the mRNA of IL-12 and decrease interferon-gamma (IFN-) producing T-cells by over 50% [71,72].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [71] Garssen, 1999, UVB exposure-induced systemic modulation of Th1- and Th2-mediated immune responses, Immunology source

      The Results report reduced cytokine mRNA expression and suppressed IFN-γ production after UVB pre-exposure in sensitized mice; the Discussion also reports suppression of IL-12 in contact-hypersensitivity models. Neither passage says that IL-12 mRNA was eliminated in T cells or that the number of IFN-γ-producing T cells fell by over 50%. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [72] Gilleaudeau, 2010, Effective narrow-band UVB radiation therapy suppresses the IL-23/IL-17 axis in normalized psoriasis plaques, J. Invest. Dermatol source

      The Results section (‘IL-17 and IL-22 were reduced in normalized plaques’; page unavailable) reports an average 85% decrease in IFN-γ after NB-UVB irradiation of PBMCs used as a surrogate source of T cells. The Results section (‘Decreased dendritic cell cytokines in normalized plaques’; page unavailable) reports reduced IL-12/23p40 mRNA in responsive skin plaques, not elimination of IL-12 mRNA in T cells. The paper also does not quantify a decrease in the number of IFN-γ-producing T cells. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Physiologically, UVR is known to induce synthesis of melanin in melanocytes, and melanin is important in the protection against harmful effects of UV.

    “Physiologically, UVR is known to induce synthesis of melanin in the melanocytes and melanin is important in the protection of harmful effects of UV (Figure 3) [75].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [75] Kobayashi, 1998, Supranuclear melanin caps reduce ultraviolet induced DNA photoproducts in human epidermis, J. Invest. Dermatol source

  • May combine two claims.

    Premisecitation

    α-MSH reduces the generation of UV-induced DNA photoproducts by enhancing nucleotide excision repair and diminishes the induction of oxidative DNA injury through elimination of ROS.

    “For example, α-MSH is known to reduce the generation of UV-induced DNA photoproducts by enhancing nucleotide excision repair (NER) and to diminish the induction of oxidative DNA injury through elimination of ROS [77,78].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [77] Smith, 2008, Melanocortin-1 receptor signaling markedly induces the expression of the NR4A nuclear receptor subgroup in melanocytic cells, J. Biol. Chem source

      The results section reports that NDP-MSH-treated human melanocytes cleared more UVB-induced cyclobutane pyrimidine dimers than vehicle-treated cells. The paper supports enhanced clearance of these DNA lesions, but does not establish reduced initial photoproduct generation, identify nucleotide excision repair as the mechanism, or report elimination of ROS and reduced oxidative DNA injury. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [78] Song, 2009, alpha-MSH activates immediate defense responses to UV-induced oxidative stress in human melanocytes, Pigment. Cell Melanoma Res source

  • May combine two claims.

    Interpretationcitation

    The fact that arsenic-induced skin cancers do not usually occur in sun-exposed skin might result from the synergistic apoptotic effects of UV and arsenic in keratinocytes, in which combined UVB irradiation and arsenic treatment results in pro-apoptotic effects induced by activation of Caspase 8 and Caspase 9.

    “The fact that arsenic-induced skin cancers do not usually occur in sun-exposed skin might result from the synergistic apoptotic effects of UV and arsenic in keratinocytes, in which the combined use of UVB irradiation and arsenic treatment results in the pro-apoptotic effects induced by activation of Caspase 8 and Caspase 9 [44,45].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [44] Lee, 2011, Aberrant immune responses in arsenical skin cancers, Kaohsiung J. Med. Sci source

      Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [45] Yu, 2006, Arsenic carcinogenesis in the skin, J. Biomed. Sci source

  • May combine two claims.

    Premisecitation

    If left unrepaired, damaged DNA, as reflected by an increase in 8-OHdG, may result in errors in DNA synthesis and genomic mutations, which may contribute to carcinogenesis in the context of active cell proliferation.

    “If left unrepaired, the damaged DNA, as reflected by an increase in 8-hydroxy-2′-deoxyguanosine (8-OHdG) [15], may result in errors in DNA synthesis and genomic mutations, which may contribute to carcinogenesis in the context of active cell proliferation.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Batista, 2009, How DNA lesions are turned into powerful killing structures: Insights from UV-induced apoptosis, Mutat. Res source

  • May combine two claims.

    Premisecitation

    UVA has the longest wavelength with the lowest energy and can penetrate deeply into the dermis and cause aging effects.

    “UVA has the longest wavelength with the lowest energy and can penetrate deeply into the dermis and cause aging effects [11].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Krutmann, 2001, The role of UVA rays in skin aging, Eur. J. Dermatol

  • May combine two claims.

    Premisecitation

    A therapeutic dosage of UV can induce cell cycle arrest, activate antioxidant and DNA repair enzymes, and induce apoptosis through translocation of Bcl-2 family proteins in melanocytes to ensure genomic integrity and survival of melanocytes.

    “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.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [76] Kadekaro, 2010, Stepping up melanocytes to the challenge of UV exposure, Pigment. Cell Melanoma Res source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Once activated by endogenous or exogenous antigens, Langerhans cells can migrate to skin draining lymph nodes and activate T cells.

    “Once activated by endogenous or exogenous antigens, they can migrate to skin draining lymph nodes and activate T cells [7].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Bennett, 2007, Langerhans cells are required for efficient presentation of topically applied hapten to T cells, J. Immunol source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Most melanocytes are distributed in basal layers, synthesize and transfer melanin to adjacent keratinocytes, and contribute to skin color and photoprotection.

    “Most of the melanocytes are distributed in basal layers, synthesizing and transferring melanin to adjacent keratinocytes, and contributing to skin color and photoprotection [5].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Wellbrock, 2007, Melanoma biology and new targeted therapy, Nature source

  • May combine two claims.

    Premisecitation

    UVR induces multimerization of CD95, resulting in its binding to FADD, followed by activation of the caspase cascade from Caspase 8 to Caspase 3.

    “UVR induce multimerization of CD95, resulting in its binding to the adaptor protein Fas-associated protein with death domain (FADD), followed by commitment activation of caspase cascade from Caspase 8 to Caspase 3 [34].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] Bang, 2003, In vivo UVB irradiation induces clustering of Fas (CD95) on human epidermal cells, Exp. Dermatol source

  • May combine two claims.

    Premisecitation

    Bcl-2 inhibits Caspase 3 and Caspase 8 activation, while Bcl-x partially inhibits cytochrome c release.

    “Bcl-2 inhibits Caspase 3 and Caspase 8 activation, while Bcl-x partially inhibits cytochrome c release [42].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Lippens, 2004, Activation of p38 MAPK is required for Bax translocation to mitochondria, cytochrome c release and apoptosis induced by UVB irradiation in human keratinocytes, FASEB J source

  • May combine two claims.

    Premisecitation

    Since UV can induce apoptosis of keratinocytes, the apoptotic body is a potent inducer for immature Langerhans cells.

    “Since UV can induce apoptosis of keratinocytes, the apoptotic body is a potent inducer for immature LCs [61].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [61] Voll, 1997, Immunosuppressive effects of apoptotic cells, Nature source

  • May combine two claims.

    Premisereasoning

    In lichenoid reactions, inflammatory skin cells line up in the superficial dermis and attack the overlying epidermis, causing scattered keratinocyte apoptosis that manifests as dyskeratotic cells and/or a cytoid body and as a positive deposition in direct immuno-fluorescent assay.

    “These inflammatory cells cause scattered keratinocyte apoptosis, which manifests itself as dyskeratotic cells and/or a cytoid body and as a positive deposition in direct immuno-fluorescent assay (DIF).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Similar to keratinocytes, UV induces cell cycle arrest, activation of antioxidant and DNA repair enzymes, and regulation of apoptotic pathways in melanocytes, to ensure genomic integrity and survival of melanocytes.

    “Similar to that seen in keratinocytes, UV induces cell cycle arrest, activation of antioxidant and DNA repair enzymes, and regulation of apoptotic pathways in melanocytes, to ensure genomic integrity and survival of melanocytes [76].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [76] Kadekaro, 2010, Stepping up melanocytes to the challenge of UV exposure, Pigment. Cell Melanoma Res source

  • May combine two claims.

    Premisecitation

    In primary keratinocytes, UVB induces keratinocyte apoptosis via suppression of Bcl-2 expression (intrinsic) and activation of Caspase 8 (extrinsic).

    “One of our previous studies showed that, in primary keratinocytes, UVB induces keratinocyte apoptosis via suppression of Bcl-2 expression (intrinsic) and activation of Caspase 8 (extrinsic) [43].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] Lee, 2004, Effects and interactions of low doses of arsenic and UVB on keratinocyte apoptosis, Chem. Res. Toxicol source

  • May combine two claims.

    Premisecitation

    When irradiated with UVA, psoralens can inhibit DNA replication and cause cell cycle arrest and ultimately apoptosis.

    “When irradiated with UVA, psoralens can inhibit DNA replication and cause cell cycle arrest and ultimately apoptosis.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [110] Lapolla, 2011, A review of phototherapy protocols for psoriasis treatment, J. Am. Acad. Dermatol source

  • May combine two claims.

    Premisecitation

    Narrowband UVB has increased efficacy in psoriasis treatment over broadband UVB and is safer than PUVA.

    “Narrowband UVB has increased efficacy in psoriasis treatment over broadband UVB and is safer than PUVA [108].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [108] Housman, 2002, Phototherapy utilization for psoriasis is declining in the United States, J. Am. Acad. Dermatol. source

  • May combine two claims.

    Premisecitation

    The balance of TRAIL death and decoy receptors might be altered by UVB irradiation, which at lower fluences might induce TRAIL-mediated apoptosis by inhibition of binding with decoy receptors.

    “This balance might be altered by UVB irradiation, which at lower fluences might induce TRAIL-mediated apoptosis by inhibition of binding with decoy receptors [38].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Qin, 2004, Low-dose UV-radiation sensitizes keratinocytes to TRAIL-induced apoptosis, J. Cell Physiol source

  • May combine two claims.

    Premisecitation

    UV-induced DNA breaks in Langerhans cells could induce suppressive cytokines such as IL-10 and inhibit contact hypersensitivity responses.

    “UV-induced DNA breaks in LCs could induce suppressive cytokines such as IL-10 and inhibit CHS responses [63].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [63] Nishigori, 1998, HindIII liposomes suppress delayed-type hypersensitivity responses in vivo and induce epidermal IL-10 in vitro, J. Immunol source

  • May combine two claims.

    Premisereasoning

    UV-induced skin cancers tend to occur solitarily in sun-exposed skin whereas arsenic-induced skin cancers tend to occur in multiplicity and are distributed in sun-spared skin.

    “UV-induced skin cancers tend to occur solitarily in sun-exposed skin whereas arsenic-induced skin cancers tend to occur in multiplicity and are distributed in sun-spared skin.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    UV can induce the activation of transcription factors USF-1, Mitf, ATF-2, Nrf-2 and p53, and inhibition of NFκB.

    “In addition to the induction of paracrine factors, UV can induce the activation of the transcription factors USF-1, Mitf, ATF-2, Nrf-2 and p53, and inhibition of NFκB [76].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [76] Kadekaro, 2010, Stepping up melanocytes to the challenge of UV exposure, Pigment. Cell Melanoma Res source

  • May combine two claims.

    Premisecitation

    Many cell types outside the skeletal system, including various cells in the skin, express the vitamin D receptor and convert circulating 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D for local use.

    “On the other hand, many cell types outside of the skeletal system, including various cells in the skin, also express the vitamin D receptor. Those cell types convert circulating 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D for local use [81].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [81] MacLaughlin, 1982, Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin, Science source

  • May combine two claims.

    Interpretationreasoning

    p53 acts as an important regulator of DNA repair but is not involved in the apoptosis of basal keratinocytes.

    “Thus, p53 acts as an important regulator of DNA repair but it is not involved in the apoptosis of basal keratinocytes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Psoralens directly interact with RNA, proteins and other cellular components and indirectly modify them via ROS.

    “Psoralens directly interact with RNA, proteins and other cellular components and indirectly modify them via ROS [112].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [112] Epstein, 1990, Phototherapy and photochemotherapy, N. Engl. J. Med source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Currently irradiations with broadband UVB, narrowband UVB, 308 nm excimer laser, UVA1, UVA with psoralen (PUVA), and extracorporeal photochemotherapy are in use.

    “Currently, irradiations with broadband UVB (290–320 nm), narrowband UVB (311–313 nm), 308 nm excimer laser, UVA 1 (340–400 nm), UVA with psoralen (PUVA), and extracorporeal photochemotherapy (photopheresis) are in use [105].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [105] Atta, 2012, The role of extracorporeal photopheresis in the treatment of cutaneous T-cell lymphomas, Transfus. Apher. Sci source

  • May combine two claims.

    Premisecitation

    Overexpression of DNA repair enzymes such as T4 endonuclease V or photolyase can efficiently repair UV-induced pyrimidine dimers and inhibit the local immunosuppression of cutaneous APCs and regulatory T cells.

    “In contrast, overexpression of DNA repair enzymes, such as T4 endonuclease V or photolyase, can efficiently repair UV-induced pyrimidine dimers and inhibit the local immunosuppression of cutaneous APCs and regulatory T cells (Treg) [64].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [64] Kripke, 1996, Role of DNA damage in local suppression of contact hypersensitivity in mice by UV radiation, Exp. Dermatol source

  • May combine two claims.

    Premisecitation

    Clinically, several diseases are treated with UVB-based phototherapy, including psoriasis, atopic dermatitis, vitiligo, cutaneous T-cell lymphomas, and morphea, because UVB affects cell proliferation, apoptosis, and immunomodulation.

    “Clinically, several diseases are treated with UVB-based phototherapy, including psoriasis, atopic dermatitis, vitiligo, cutaneous T-cell lymphomas, and morphea [98] because UVB have an effect on cell proliferation, apoptosis, and immunomodulation.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [98] Raulin, 1998, Q-switched ruby laser treatment of tattoos and benign pigmented skin lesions: A critical review, Ann. Plast. Surg source

  • May combine two claims.

    Premisecitation

    UV induces apoptosis, resulting in the generation of chemokines, which recruit more effector memory T cells and plasmacytoid dendritic cells in UV-induced cutaneous lupus erythematosus lesions.

    “UV induces apoptosis, resulting in the generation of chemokines, which recruit more effector memory T cells and plasmacytoid DCs in UV-induced cutaneous LEs lesions [116].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Lehmann, 2009, Clinic and pathophysiology of photosensitivity in lupus erythematosus, Autoimmun. Rev source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Mutations in the NER machinery can cause xeroderma pigmentosum, an autosomal recessive disease with impaired DNA repair after UV radiation and early development of skin cancers.

    “The mutations in the NER machinery can cause xeroderma pigmentosum (XP), an autosomal recessive disease with impaired DNA repair after UV radiation and early development of skin cancers [30].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Hoeijmakers, 2009, DNA damage, aging, and cancer, N. Engl J. Med source

  • May combine two claims.

    Premisecitation

    Photodynamic therapy utilizes an exogenous photosensitizer that is preferentially absorbed by tumor cells, endothelial cells, and active inflammatory cells; once irradiated, target cells are destroyed by production of ROS and execution of the apoptotic cascade.

    “Photodynamic therapy (PDT) utilizes an exogenous photosensitizer that is preferentially absorbed by tumor cells, endothelial cells, and active inflammatory cells. Once the cells harboring the photosensitizer are irradiated with light fitting the absorption spectrum, the target cells are destroyed by production of ROS and execution of the apoptotic cascade.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [104] Lan, 2006, Low-energy helium-neon laser induces locomotion of the immature melanoblasts and promotes melanogenesis of the more differentiated melanoblasts: Recapitulation of vitiligo repigmentation in vitro, J. Invest. Dermatol source

  • May combine two claims.

    Premisecitation

    Vitamin D is best synthesized by the skin following UVB exposure, and this synthesis may vary among individuals with different skin types.

    “Vitamin D is best synthesized by the skin following UVB exposure [81] and this synthesis may vary among individuals with different skin types [82].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [81] MacLaughlin, 1982, Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin, Science source
    • cites [82] Scanlon, 2002, Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: Third National Health and Nutrition Examination Survey, 1988–1994, Am. J. Clin. Nutr source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisereasoning

    Due to its potent effect in inducing lymphocyte apoptosis, extracorporeal photopheresis is used to treat erythrodermic cutaneous lymphomas.

    “Due to its potent effect in inducing lymphocyte apoptosis, extra-corporeal photopheresis is used to treat erythrodermic cutaneous lymphomas.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Basal keratinocytes exhibit p53-independent apoptosis following UV radiation, but upon induction of differentiation to committed progenitor cells, the apoptosis is dependent on p53-related signaling pathway.

    “On the other hand, basal keratinocytes also exhibit p53-independent apoptosis (described below) following UV radiation. However, upon induction of differentiation to committed progenitor cells, the apoptosis is dependent on p53-related signaling pathway.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The dynamics of melanogenesis induced by repeated exposures depends on UV dose, dose interval and emission spectrum, with UVA generally being stronger than UVB to induce pigmentations.

    “The dynamics of melanogenesis induced by repeated exposures depends on UV dose, dose interval and emission spectrum with UVA generally being stronger than UVB to induce pigmentations [79].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [79] Ravnbak, 2007, Pigmentation after single and multiple UV-exposures depending on UV-spectrum, Arch. Dermatol. Res source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Visible light in the blue-green range (430-490 nm) has been used as a standard treatment of neonatal jaundice; tissue bilirubin absorbs the light and the metabolites become more lipophilic and more readily excreted.

    “Visible light in the blue-green range (430–490 nm) has been used as a standard treatment of neonatal jaundice, for example. The tissue bilirubin, possessing the heme group, absorbs the light in this spectrum and the metabolites become more lipophilic than the mother compound and are more readily excreted [92].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [92] Moller, 2005, How Finsen’s light cured lupus vulgaris, Photodermatol. Photoimmunol. Photomed source

  • May combine two claims.

    Premisecitation

    Epidermal and dermal infiltrating lymphocytes are robustly suppressed by PUVA, with varying effects on different T-cell subsets.

    “Epidermal and dermal infiltrating lymphocytes are robustly suppressed by PUVA, with varying effects on different T-cell subsets [113].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [113] Mermelstein, 1989, Inhibition of epidermal growth factor receptor tyrosine kinase activity in A431 human epidermoid cells following psoralen/ultraviolet light treatment, Mol. Pharmacol source

  • May combine two claims.

    Premisecitation

    UVA1 exerts its therapeutic effects through T cell apoptosis, collagenase induction, angiogenesis, and tissue remodeling.

    “UVA1 exerts its therapeutic effects through T cell apoptosis, collagenase induction, angiogenesis, tissue remodeling [97].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [97] Hunzeker, 2010, Treatment of superficial infantile hemangiomas of the eyelid using the 595-nm pulsed dye laser, Dermatol. Surg source

  • May combine two claims.

    Premisecitation

    Like UVB, PUVA can also stimulate melanogenesis and inhibit immune responses.

    “Like UVB, PUVA can also stimulate melanogenesis and inhibit immune responses [114].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [114] Averbeck, 1989, Recent advances in psoralen phototoxicity mechanism, Photochem. Photobiol source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The most widely used photosensitizer is ALA, which can convert to porphyrins in the tissue.

    “The most widely used photosenstizer is ALA, which can convert to porphyrins in the tissue [115].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [115] Volkmar, 2010, UVA-induced phenoxyl radical formation: A new cytotoxic principle in photodynamic therapy, Free Radic Biol. Med source

  • May combine two claims.

    Interpretationnone given

    The articles reviewed in this study suggest that DNA damage, induction of apoptosis, immune suppression, alteration in cytokine profiles, and induction of cell signaling pathways may contribute to the effects of UV-based phototherapy.

    “The articles reviewed in this study suggest that DNA damage, induction of apoptosis, immune suppression, alteration in cytokine profiles, and induction of cell signaling pathways may contribute to the effects of UV-based phototherapy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In peripheral sensory nerves, UVR enhances stimulation of sensory nerves and increases production of neuropeptides, prompting recall immunological response.

    “In peripheral sensory nerves, UVR enhances stimulation of sensory nerves and increases production of neuropeptides, prompting recall immunological response [130].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [130] Howes, 2006, Topical capsaicin reduces ultraviolet radiation-induced suppression of Mantoux reactions in humans, J. Dermatol. Sci source

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    UV radiation can also cause damage to the molecular targets located in the cytosol and cell membranes of keratinocytes.

    “UV radiation can also cause damage to the molecular targets located in the cytosol and cell membranes of keratinocytes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    UV may result in the depletion of epidermal LCs and dermal T lymphocytes, which then lead to Treg activation in the lymph nodes.

    “UV may result in the depletion of epidermal LCs and dermal T lymphocytes, which then lead to Treg activation in the lymph nodes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    The absorption of UV in endothelial cells preferentially uptaking porphyrins might help explain the therapeutic base for photodynamic therapy.

    “The absorption of UV in endothelial cells preferentially uptaking porphyrins might help explain the therapeutic base for photodynamic therapy.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    UV radiation is absorbed by nuclear DNA, initiating a cascade of apoptotic events by forming DNA photoproducts and suppressing DNA synthesis.

    “UV radiation is absorbed by nuclear DNA, initiating a cascade of apoptotic events by forming DNA photoproducts and suppressing DNA synthesis.”
    Quote in the paperNot a substantial claim
62 of 62

  • The paper relies on this without support.

    Physiological apoptosis is important in governing normal skin turnover.

    “Physiological apoptosis is important in governing normal skin turnover.”

  • The paper relies on this without support.

    Pathological apoptosis may lead to benign proliferative inflammatory disease (such as psoriasis vulgaris) and neoplastic growth.

    “The pathological apoptosis, on the other hand, may lead to benign proliferative inflammatory disease (such as psoriasis vulgaris) and neoplastic growth.”

  • The paper relies on this without support.

    Melanins, produced by melanocytes, play an important role in protecting the skin against UV radiation.

    “Melanins, produced by melanocytes, play an important role in protecting the skin against UV radiation.”

  • The paper relies on this without support.

    Skin cancers occur more often in individuals with light skin.

    “Skin cancers occur more often in individuals with light skin.”

  • The paper relies on this without support.

    UVA1 radiation induces collagenase (matrix metalloproteinase-1) expression, T-cell apoptosis, and depletes Langerhans and mast cells in the dermis.

    “UVA1 radiation induces collagenase (matrix metalloproteinase-1) expression, T-cell apoptosis, and depletes Langerhans and mast cells in the dermis.”
5 of 5

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Self-check results appear here once an independent check has confirmed them.

Cited works that were retracted

Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.

  • Cites a retracted work: 10.1016/s0014-5793(03)00238-2

    Info

    The cited work was retracted on 2025-02-26 (notice 10.1002/1873-3468.70019), not before this paper was published (2013-03-20).

    Cited work 10.1016/s0014-5793(03)00238-2 · retracted 2025-02-26 · notice 10.1002/1873-3468.70019 · this paper published 2013-03-20

1 of 1

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Related

Authors
Lee, C.-H., Wu, S.-B., Hong, C.-H., Yu, H.-S., & Wei, Y.-H.
Affiliations
  • Kaohsiung Medical University (TW)
  • National Yang Ming University (TW)
  • Kaohsiung Veterans General Hospital (TW)
  • Mackay Medical University (TW)
Corresponding author
Wei, Yau-Huei
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2013-03-20
Volume
14
Issue
3
Pages
6414-6435
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms14036414
PMC
PMC3634415
OpenAlex
W2161464421
Semantic Scholar
6ca3f06a91504b5552f9f530bfc109ff6f72e165
Cited by
271
References
134
Citations by year
2026: 18 · 2025: 27 · 2024: 18 · 2023: 19 · 2022: 28 · 2021: 26 · 2020: 19 · 2019: 12 · 2018: 15 · 2017: 24 · 2016: 24 · 2015: 17 · 2014: 16 · 2013: 6
FWCI
24.51
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Science Council (NSC 100, NSC95-2314-B-037-024, NSC96‐2314‐B‐037‐043, NSC100-2320-B-010-024-MY3, NSC95)
  • Kaohsiung Medical University (KMU‐QA096005)
  • National Health Research Institutes (NHRI-EO-096-PP-11, NHRI CN-PD-9611P)
  • Mackay Medical College
Topics
  • Health Sciences › Medicine › Dermatology › Skin Protection and Aging
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
Keywords
ultraviolet radiation, UV-induced apoptosis, keratinocytes, Langerhans cells, melanocytes, phototherapy, death receptors, reactive oxygen species, RANK signaling, Bcl-2 family proteins, regulatory T cells, immunosuppression, melanogenesis, vitamin D synthesis, DNA repair, cell cycle arrest, immunomodulation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-28.

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