Identification of Genes Responsive to Solar Simulated UV Radiation in Human Monocyte-Derived Dendritic Cells

Ultraviolet (UV) irradiation has profound effects on the skin and the systemic immune system. Several effects of UV radiation on Dendritic cells (DCs) functions have been described. However, gene expression changes induced by UV radiation in DCs have not been addressed before. In this report, we irradiated human monocyte-derived DCs with solar-simulated UVA/UVB and analyzed regulated genes on human whole genome arrays. Results were validated by RT-PCR and further analyzed by Gene Set Enrichment Analysis (GSEA). Solar-simulated UV radiation up-regulated expression of genes involved in cellular stress and inflammation, and down-regulated genes involved in chemotaxis, vesicular transport and RNA processing. Twenty four genes were selected for comparison by RT-PCR with similarly treated human primary keratinocytes and human melanocytes. Several genes involved in the regulation of the immune response were differentially regulated in UVA/UVB irradiated human monocyte-derived DCs, such as protein tyrosine phosphatase, receptor type E (PTPRE), thrombospondin-1 (THBS1), inducible costimulator ligand (ICOSL), galectins, Src-like adapter protein (SLA), IL-10 and CCR7. These results indicate that UV-exposure triggers the regulation of a complex gene repertoire involved in human-DC–mediated immune responses.     

The mechanisms of action of phototherapy in the treatment of the most common dermatoses

Phototherapy denotes the use of ultraviolet (UV) light in the management of several dermatoses. Most phototherapy regimens utilize ultraviolet radiation of different wavelenghts. 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 being used. The interplay of the various photobiologic pathways is far from being completely understood. Disordes that may benefit from such approach are numerous, with psoriasis, atopic dermatitis, cutaneous T-cell lymphomas, morphea, and vitiligo as main indications. The immunomodulatory effects of UVB radiation primarily affect the epidermis and superficial dermis, while UVA radiation affects mid and deep dermal components, especially blood vessels. UVB radiation is absorbed by endogenous chromophores, such as nuclear DNA, which initiates a cascade of events. Absorption of UV light by nucleotides causes the formation of DNA photoproducts and suppresses DNA synthesis. In addition UV light stimulates synthesis of prostaglandins and cytokines that play important roles in immune suppression. It may reduce the number of Langerhans cells, cutaneous T lymphocytes and mast cells in the dermis. UV radiation can also affect extranuclear molecular targets located in the cytoplasm and cell membrane. Immune suppression, alteration in cytokine expression, and cell cycle arrest may all contribute to the suppression of disease activity. PUVA is a form of chemophototherapy which uses UVA light to activate chemicals known as psoralens, hence psoralen ultraviolet A. The conjunction of psoralens with epidermal DNA inhibits DNA replication and causes cell cycle arrest. Psoralen photosensitization also causes an alteration in the expression of cytokines and cytokine receptors. Psoralens interact with RNA, proteins and other cellular components and indirectly modify proteins and lipids via singlet oxygen-mediated reactions or by generating of free radicals. Infiltrating lymphocytes are strongly suppressed by PUVA, with variable effects on different T-cell subsets. Psoralens and UV radiation also stimulate melanogenesis. Extracorporeal photopheresis is technique used in treatment of erythrodermic cutaneous lymphomas. It is very potent in induction of lymphocyte apoptosis. Despite the introduction of numerous effective systemic medications and biologic agents in dermatology, phototherapy remains a reliable, and often preferred option for several dermatoses.     

Effects of ultraviolet B irradiation on cutaneous leishmaniasis

Protection against many infectious diseases is mediated by cellular immunity in the competent host. Ultraviolet (UV) radiation, a component of sunlight, is a potent suppressor of cell-mediated immune responses. Suzanne Holmes Giannini discusses the possible relevance of ambient levels of UVB to pathogenesis and immunity in infectious diseases, with special reference to cutaneous leishmaniasis.     

An Arabidopsis Mutant Tolerant to Lethal Ultraviolet-B Levels Shows Constitutively Elevated Accumulation of Flavonoids and Other Phenolics

The isolation and characterization of mutants hypersensitive to ultraviolet (UV) radiation has been a powerful tool to learn about the mechanisms that protect plants against UV-induced damage. To increase our understanding of the various mechanisms of defense against UVB radiation, we searched for mutations that would increase the level of tolerance of Arabidopsis plants to UV radiation. We describe a single gene dominant mutation (uvt1) that leads to a remarkable tolerance to UVB radiation conditions that would kill wild-type plants. Pigment analyses show a constitutive increase in accumulation of UV-absorbing compounds in uvt1 that increases the capacity of the leaves to block UVB radiation and therefore is likely to be responsible for the elevated resistance of this mutant to UVB radiation. These increases in absorption in the UV region are due, at least in part, to increases in flavonoid and sinapate accumulation. Expression of chalcone synthase (CHS) mRNA was shown to be constitutively elevated in uvt1 plants, suggesting that the increases in absorption may be a consequence of changes in gene expression. Expression of CHS in uvt1 was shown to be still inducible by UV, indicating that the uvt1 lesion may not affect the UV-mediated regulation of CHS gene expression. Our data support an important role for UV screens in the overall protection of plants to UVB radiation. The uvt1 mutant could prove to be an important tool to elucidate further the exact role of UV-absorbing pigments in UV protection as well as the relative contribution of other mechanisms to the overall tolerance of plants to UV radiation.     

Ultraviolet radiation,resistance to infectious diseases,and vaccination responses

Exposure to ultraviolet (UV) radiation, as in sunlight, can modulate immune responses in animals and humans. This immunomodulation can lead to positive health effects especially with respect to certain autoimmune diseases and allergies. However, UV-induced immunomodulation has also been shown to be deleterious. Experimental animal studies have revealed that UV exposure can impair resistance to many infectious agents, such as bacteria, parasites, viruses, and fungi. Importantly, these effects are not restricted to skin-associated infections, but also concern systemic infections. The real consequences of UV-induced immunomodulation on resistance to infectious diseases are not known for humans. Risk estimations have been performed through extrapolation of animal data, obtained from infection models, to the human situation. This estimation indicated that UV doses relevant to outdoor exposure can impair the human immune system sufficiently to have effects on resistance to infections. To further quantify and validate this risk estimation, data, e.g., from human volunteer studies, are necessary. Infection models in humans are not allowed for ethical reasons. However, vaccination against an infectious disease evokes a similar immune response as the pathogen and thereby provides an opportunity to measure the effect of UV radiation on the immune system and an estimate of the possible consequences of altered resistance to infectious agents. Effects of controlled UVB exposure on immune responses after hepatitis B vaccination have been established in mice and human volunteers. In mice, cellular and Th1-associated humoral immune responses to hepatitis B were significantly impaired, whereas in human volunteers no significant effect of UVB on these responses could be found. Preliminary data indicate that cytokine polymorphisms might be, at least in part, responsible for interindividual differences in immune responses and in susceptibility to UVB-induced immunomodulation. In addition, adaptation to UV exposure needs to be considered as a possible explanation for the difference between mice and humans that was observed in the hepatitis B vaccination model.     

Comparison of the impacts of consumers, ambient UV, and future UVB irradiance on mid-latitudinal macroepibenthic assemblages

Future levels in ultraviolet-B (UVB) radiation are expected to increase directly due to stratospheric ozone depletion and under water indirectly by, for example, global warming effects on DOC concentrations, altered trophic interactions in the plankton, or reduced eutrophication. While detrimental UV effects have been reported at the cellular level, little to nothing is known about community-wide effects of ambient and future UVB radiation. In a 4-month field experiment, the ambient UV regime was (i) reduced by cut-off filters which removed either UVB or total UV from the solar spectrum or (ii) increased to predicted future levels by UVB lamps. To allow relating the effects of present and future UV regimes to another important ecological control of community structure and diversity in subtidal marine habitats, consumer effects were quantified by an exclusion treatment under ambient light regimes. Ambient UV regimes did not affect community structure, biomass accrual, and diversity. In contrast, under enhanced UVB levels, the dominance of the competitively superior blue mussels increased and species richness and biomass accrual decreased. Species composition of the assemblages differed between the two UV regimes. Effects of enhanced UVB radiation and of consumption on biomass accrual, diversity, and structure of the community were comparable in magnitude and timing, but of opposite direction. In contrast, the effects of enhanced UVB radiation on growth and abundance of mussels were in the same direction, but shorter and weaker than consumer effects. Most UV effects were transitory and vanished within the first 2 months of succession. Our results indicate that present and future UVB levels may be of limited importance and not stronger in effect size than other ecological controls in structuring the shallow-water low-diversity macrobenthic communities in temperate regions.     

Understanding the connection between platelet-activating factor,a UV-induced lipid mediator of inflammation,immune suppression and skin cancer

Lipid mediators of inflammation play important roles in several diseases including skin cancer, the most prevalent type of cancer found in the industrialized world. Ultraviolet (UV) radiation is a complete carcinogen and is the primary cause of skin cancer. UV radiation is also a potent immunosuppressive agent, and UV-induced immunosuppression is a well-known risk factor for skin cancer induction. An essential mediator in this process is the glyercophosphocholine 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine commonly referred to as platelet-activating factor (PAF). PAF is produced by keratinocytes in response to diverse stimuli and exerts its biological effects by binding to a single specific G-protein-coupled receptor (PAF-R) expressed on a variety of cells. This review will attempt to describe how this lipid mediator is involved in transmitting the immunosuppressive signal from the skin to the immune system, starting from its production by keratinocytes, to its role in activating mast cell migration in vivo, and to the mechanisms involved that ultimately lead to immune suppression. Recent findings related to its role in regulating DNA repair and activating epigenetic mechanisms, further pinpoint the importance of this bioactive lipid, which may serve as a critical molecular mediator that links the environment (UVB radiation) to the immune system and the epigenome.     

The interaction of UVA and UVB wavebands with particular emphasis on signalling

The molecular response mechanisms and signalling pathways activated upon exposure to ultraviolet (UV) radiation have been extensively studied within the last two decades. Although many signalling pathways can be activated by both UVA as well as UVB, there are several distinctions indicating wavelength-specific response patterns accommodated by the terms UVA response and UVB response. Given that human skin is primarily exposed to UV light from solar radiation consisting of both UVA and UVB, we sought to explore a potential interaction between the distinct UVA and UVB responses at the level of MAPK. Our results indicate that the two distinct stress responses elicited by UVA or UVB interact with each other, producing a "third" response that is different from either alone and cannot be explained by a simple addition of effects.     

Cytokine polymorphisms play a role in susceptibility to ultraviolet B-induced modulation of immune responses after hepatitis B vaccination

UVB exposure can alter immune responses in experimental animals and humans. In an earlier human volunteer study, we demonstrated that hepatitis B-specific humoral and cellular immunity after vaccination on average were not significantly affected by UVB exposure. However, it is known that individuals differ in their susceptibility to UVB-induced immunomodulation, and it was hypothesized that polymorphisms in specific cytokines may play a role in this susceptibility. In this respect, we previously demonstrated that immune responses after hepatitis B vaccination are influenced by the minor allelic variant of IL-1 beta in the general population. For all volunteers, single nucleotide polymorphisms were determined for the following UV response-related cytokines: IL-1 receptor antagonist (+2018), IL-1 alpha (+4845), IL-1 beta (+3953), TNF-alpha (-308), and TNF-alpha (-238). Exposure to UVB significantly suppressed Ab responses to hepatitis B in individuals with the minor variant for the IL-1 beta polymorphism. Increased minimal erythema dose values (just perceptible), which resulted in higher absolute UVB exposures, were observed in the same individuals. There were no associations observed between UVB-induced immunomodulation and the other cytokine polymorphisms examined. This study indicates that individual susceptibility to UVB radiation needs to be considered when studying the effects of UVB in humans.     

Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis

Ultraviolet (UV) radiation causes inflammation, gene mutation and immunosuppression in the skin. These biological changes are responsible for photocarcinogenesis. UV radiation in sunlight is divided into two wavebands, UVB and UVA, both of which contribute to these biological changes, and therefore probably to skin cancer in humans and animal models. Oxidative damage caused by UV contributes to inflammation, gene mutation and immunosuppression. This article reviews evidence for the hypothesis that UV oxidative damage to these processes contributes to photocarcinogenesis. UVA makes a larger impact on oxidative stress in the skin than UVB by inducing reactive oxygen and nitrogen species which damage DNA, protein and lipids and which also lead to NAD+ depletion, and therefore energy loss from the cell. Lipid peroxidation induces prostaglandin production that in association with UV-induced nitric oxide production causes inflammation. Inflammation drives benign human solar keratosis (SK) to undergo malignant conversion into squamous cell carcinoma (SCC) probably because the inflammatory cells produce reactive oxygen species, thus increasing oxidative damage to DNA and the immune system. Reactive oxygen or nitrogen appears to cause the increase in mutational burden as SK progress into SCC in humans. UVA is particularly important in causing immunosuppression in both humans and mice, and UV lipid peroxidation induced prostaglandin production and UV activation of nitric oxide synthase is important mediators of this event. Other immunosuppressive events are likely to be initiated by UV oxidative stress. Antioxidants have also been shown to reduce photocarcinogenesis. While most of this evidence comes from studies in mice, there is supporting evidence in humans that UV-induced oxidative damage contributes to inflammation, gene mutation and immunosuppression. Available evidence implicates oxidative damage as an important contributor to sunlight-induced carcinogenesis in humans.     

Synergistic interplay of UV radiation and urban particulate matter induces impairment of autophagy and alters cellular fate in senescence-prone human dermal fibroblasts

Skin aging is a complex process influenced by intrinsic factors and environmental stressors, including ultraviolet (UV) radiation and air pollution, among others. In this study, we investigated the effects of UVA and UVB radiation, combined with urban particulate matter (UPM), on human dermal fibroblasts (HDF). We show here that treatment of HDF with a subcytotoxic dose of UVA/UVB results in a series of events leading to mitochondrial dysfunction, increased ROS levels, and DNA damage. These effects are known to trigger either cellular senescence or cell death, depending on the cells' ability to clear damage by activating autophagy. Whereas UPM treatment in isolation did not affect proliferation or survival of HDF, of note, simultaneous UPM treatment of UV-irradiated cells selectively inhibited autophagic flux, thereby changing cell fate of a fraction of the cell population from senescence to apoptotic cell death. Our findings highlight the synergistic effects of UV radiation and UPM on skin aging, emphasizing the need to consider these factors in assessing the impact of environmental stressors on human health and opening opportunities for developing comprehensive approaches to protect and preserve skin integrity in the face of growing environmental challenges.     

Different sensitivity of carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss) to the immunomodulatory effects of UVB irradiation

In order to study the sensitivity of two fish species, carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss), to the immunomodulatory effects of ultraviolet B (UVB) radiation, the fish were exposed to a single UVB dose of 50, 250, 500 or 1,000 mJ cm(-2). These species represent different phylogenetic groups of fish, and they differ also in their behaviour inhabitating often dark and turbid (carp) or clear and transparent waters (salmonids). Immune responses were studied on day 1 post-irradiation. Unexposed fish, and fish exposed to radiation depleted of UV wavelengths served as controls. UVB irradiation markedly enhanced the blood respiratory burst and cytotoxic activity in carp, but in the head kidney these parameters were significantly suppressed. Rainbow trout respiratory burst was affected only after exposure with the highest dose of UVB. Lymphopenia and granulophilia were noted in both fish blood after exposure. This study indicates that UVB irradiation modulates immune functions in both fish species studied, and that rainbow trout is more tolerant than carp against UVB. Fish are clearly adapted to the environmental UVB levels prevailing in their usual living habitats, but are also a target of undesired effects of UVB on immune functions whenever exposed to increased radiation levels.     

Abscisic acid is involved in the response of Arabidopsis mutant sad2-1 to ultraviolet-B radiation by enhancing antioxidant enzymes

In this study, we examined the physiological mechanisms in the responses of Arabidopsis mutant sensitive to ABA and drought 2–1 (sad2-1) to ultraviolet-B radiation (UVB) treatments. The effects of enhanced UVB radiation on plant growth, concentration of UV-absorbing compounds, photosynthesis, endogenous ABA and antioxidant system were investigated in two types of Arabidopsis thaliana — the mutant sad2-1 and the wild type (WT, C24). Results indicated that, under UVB radiation, mutant sad2-1 showed a higher resistance than C24 through accumulating more UV absorption materials, maintaining bio-membrane balance and photosynthesis efficiency, enhancing endogenous ABA content and activating ROS scavenging enzymes. It can be postulated that ABA might participate in a complex signal crosstalk in increasing the tolerance of UVB.     

Immobile and tough versus mobile and weak: effects of ultraviolet B radiation on eggs and larvae of Manduca sexta

Although indirect effects of solar ultraviolet (UV) radiation on insects are well known (e.g. UV radiation can modify plant chemistry), direct effects of solar radiation on insects have received little attention. Radiation in the UVB range (300–320 nm) is damaging because it is absorbed directly by proteins and DNA. UVB should be toughest on immobile or small life stages, such as eggs or early larval instars. In the present study, the effects of UVB radiation on eggs and larvae of the tobacco hornworm Manduca sexta L. (Lepidoptera: Sphingidae) are examined. The present study aimed to address: what natural levels of UV do they experience; how does UVB affect the performance of eggs; and how does it affect the performance of larvae? In addition, do M. sexta larvae use behaviour to avoid UVB exposure and, consequently, are they physiologically less robust to UVB? In these experiments, eggs and late larval instars of M. sexta are found to be robust to natural levels of UV radiation. By contrast, young larvae are not only more susceptible to damage from UVB, but also they use behavioural means to avoid it. The strategy of using behaviour may relax selection pressures on morphological and physiological mechanisms for preventing (or recovering from) damage by environmental UV radiation.     

The greater lethality of UVB radiation to cultured human cells is associated with the specific activation of a DNA damage-independent signaling pathway

UV radiation causes cell death through the activation of various intracellular signaling molecules in both DNA damage-dependent and -independent manners. The ability of middle-wavelength UV (UVB) radiation to form DNA photoproducts is less than that of short-wavelength UV (UVC) radiation; however, the differences between UVB and UVC radiation in the extent of DNA damage-independent signaling and its contribution to cell death have not been well characterized. When cells were irradiated with UVB or UVC radiation at doses that generated equivalent amounts of DNA photoproducts, UVB radiation induced more clonogenic cell death, apoptotic cells, mitochondrial cytochrome C release, and intracellular oxidative stress. Among the signaling molecules examined, levels of p53 phosphorylated at Ser-392 and p38 were higher in UVB-irradiated cells than in UVC-irradiated cells. Both phosphorylations were reduced by treating cells with an antioxidant. Furthermore, an inhibitor of p38 also blocked the phosphorylation of p53 at Ser-392. These results suggest that UVB radiation activates the p38 pathway through the generation of oxidative stress, which merges with the DNA p53 pathway by phosphorylation of p53 at ser392. This greater contribution of the DNA damage-independent pathway in UVB-irradiated cells may explain the greater lethality of UVB radiation.     

Stem phototropism toward blue and ultraviolet light

Positive phototropism is the process through which plants orient their organs toward a directional light source. While the blue light receptors phototropins (phot) play a major role in phototropism toward blue (B) and ultraviolet (UV) radiation, recent research showed that the UVB light receptor UVR8 also triggers phototropism toward UVB. In addition, new details of the molecular mechanisms underlying the activity of these receptors and interaction with other environmental signals have emerged in the past years. In this review, we summarize the current knowledge about hypocotyledoneous and inflorescence stem growth reorientation toward B and UVB, with a focus on the molecular mechanisms.     

The mechanisms of UV radiation in the development of malignant melanoma

The sunlight was one of the first agents recognized to be carcinogenic for humans. There is convincing evidence from epidemiologic studies that exposure to solar radiation is the major cause of cutaneous melanoma in light-pigmented populations and plays a role in the increasing incidence of this malignancy. The molecular mechanisms by which UV radiation exerts its varied effects are not completely understood, however, it is considered that UVA and UVB are equally critical players in melanoma formation. Whereas UVA can indirectly damage DNA through the formation of reactive oxygen radicals, UVB can directly damage DNA causing the apoptosis of keratinocytes by forming the sunburn cells. Besides action through mutations in critical regulatory genes, UV radiation may promote cancer through indirect mechanisms, e.g. immunosuppression and dysregulation of growth factors. The carcinogenic process probably involves multiple sequential steps, some, but not all of which involve alterations in DNA structure.