The Damaging Effects of Long UVA (UVA1) Rays: A Major Challenge to Preserve Skin Health and Integrity.

Within solar ultraviolet (UV) light, the longest UVA1 wavelengths, with significant and relatively constant levels all year round and large penetration properties, produce effects in all cutaneous layers. Their effects, mediated by numerous endogenous chromophores, primarily involve the generation of reactive oxygen species (ROS). The resulting oxidative stress is the major mode of action of UVA1, responsible for lipid peroxidation, protein carbonylation, DNA lesions and subsequent intracellular signaling cascades. These molecular changes lead to mutations, apoptosis, dermis remodeling, inflammatory reactions and abnormal immune responses. The altered biological functions contribute to clinical consequences such as hyperpigmentation, inflammation, photoimmunosuppression, sun allergies, photoaging and photocancers. Such harmful impacts have also been reported after the use of UVA1 phototherapy or tanning beds. Furthermore, other external aggressors, such as pollutants and visible light (Vis), were shown to induce independent, cumulative and synergistic effects with UVA1 rays. In this review, we synthetize the biological and clinical effects of UVA1 and the complementary effects of UVA1 with pollutants or Vis. The identified deleterious biological impact of UVA1 contributing to clinical consequences, combined with the predominance of UVA1 rays in solar UV radiation, constitute a solid rational for the need for a broad photoprotection, including UVA1 up to 400 nm.

Ameliorative effect of green odor against UVB-induced immunosuppression of contact hypersensitivity.

Ultraviolet (UV) irradiation to the eye induces photoimmunosuppression. In here, we examined the effect of green odor against immunosuppression of contact hypersensitivity in the eye induced by ultraviolet B (UVB) irradiation. Systemic immunosuppression was induced in ICR mice sensitized with 0.5% oxazolone through the skin by a single exposure to UVB. Consecutive green odor treatment significantly counteracted UVB irradiation-induced immunosuppression of the contact hypersensitivity (CHS) response. The green odor treatment increased dopamine and ß-endorphin levels in the brain and the plasma, respectively, and decreased the plasma corticosterone concentration in the oxazolone-sensitized mice after UVB irradiation to the eye, in contrast with that in acetone-treated mice (treatment negative control). Green odor prevented UVB irradiation-induced photoimmunosuppression of the CHS response by regulating the dopamine/ß-endorphin/corticosterone pathway.

Photodermatitis for the Allergist.

PURPOSE OF REVIEW: The photodermatoses represent a group of disorders of sensitivity to light that continue to pose difficulties in diagnosis and management. Photodermatoses are of interest to allergists because many photosensitive skin disorders have immunologic underpinnings, and patients often present to clinic complaining of "allergy" to the sun. We provide a concise reference for allergists on the clinical recognition and management of photodermatitis. RECENT FINDINGS: New developments in the understanding of immunomodulatory effects of light have demonstrated normally immunosuppressive responses in the skin to light exposure, and a blunted immunosuppressive response in the pathogenesis of many photodermatoses. Vitamin D plays an important role in immunomodulation and itself may be affected by photodermatoses due to the impact of photoprotective treatment strategies on circulating vitamin D levels. The elucidation of the immunological basis of many photodermatoses may provide guidance for developing new treatment modalities. Further research is necessary to determine the optimal management of vitamin D metabolism in patients with photodermatoses.

Ultraviolet radiation and the skin: Photobiology and sunscreen photoprotection.

The efficacy of sunscreens can be measured by different methods, involving in vitro, ex vivo, or in vivo techniques. There is a need for a worldwide standardization of these methods to avoid misunderstanding and confusion among sunscreen users. The clinical benefits of sunscreens have been demonstrated in randomized controlled trials that established the role of sunscreens in the prevention of actinic keratoses, squamous cell carcinomas, nevi, and melanomas. Sunscreens also prevent photoimmunosuppression and signs of photoaging. Continued efforts in public education on the proper application of sunscreens and the practice of photoprotection in general are needed.

Effect of oral eicosapentaenoic acid on epidermal Langerhans cell numbers and PGD2 production in UVR-exposed human skin: a randomised controlled study.

Langerhans cells (LCs) are sentinels of skin's immune system, their loss from epidermis contributing to UVR suppression of cell-mediated immunity (CMI). Omega-3 polyunsaturated fatty acids show potential to reduce UVR suppression of CMI in mice and humans, potentially through modulation of LC migration. Our objectives were to examine whether eicosapentaenoic acid (EPA) ingestion influences UV-mediated effects on epidermal LC numbers and levels of immunomodulatory mediators including prostaglandin (PG)D2 , which is expressed by LC. In a double-blind randomised controlled study, healthy individuals took 5-g EPA-rich (n=40) or control (n=33) lipid for 12 weeks; UVR-exposed and unexposed skin samples were taken pre- and postsupplementation. Epidermal LC numbers were assessed by immunofluorescence for CD1a, and skin blister fluid PG and cytokines were quantified by LC-MS/MS and Luminex assay, respectively. Presupplementation, UVR reduced mean (SEM) LC number/mm2 from 913 (28) to 322 (40) (P<.001), and mean PGD2 level by 37% from 8.1 (11.6) to 5.1 (5.6) pg/µL; P<.001), while IL-8 level increased (P<.001). Despite confirmation of EPA bioavailability in red blood cells and skin in the active group, no between-group effect of EPA was found on UVR modulation of LC numbers, PGD2 or cytokine levels postsupplementation. Thus, no evidence was found for EPA reduction of photoimmunosuppression through an impact on epidermal LC numbers. Intriguingly, UVR exposure substantially reduced cutaneous PGD2 levels in humans, starkly contrasting with reported effects of UVR on other skin PG. Lowered PGD2 levels could reflect LC loss from the epidermis and/or altered dendritic cell activity and may be relevant for phototherapy of skin disease.

Nutritional abrogation of photoimmunosuppression: in vivo investigations.

Skin cancer is a major public health concern, and the primary aetiological factor in the majority of skin cancers is ultraviolet radiation (UVR) exposure. UVR not only induces potentially mutagenic DNA damage but also suppresses cell-mediated immunity (CMI), allowing cancerous cells to escape destruction and progress to tumours. A considerable proportion of an individual's annual sun exposure is obtained outside the vacation period when topical and physical measures for photoprotection are irregularly used. Certain nutrients could provide an adjunctive protective role, and evidence is accruing from experimental studies to support their use in abrogation of photoimmunosuppression. Moreover, developments in clinical research methods to evaluate impact of solar-simulated radiation on cutaneous CMI allow the immune protective potential of nutritional agents to be examined in humans in vivo. This article summarises the mediation of CMI and its suppression by UVR, evaluates the methodology for quantitative assessment in vivo, reviews the human studies reported on nutritional abrogation of photoimmunosuppression including recent randomized controlled trials and discusses the mechanisms of photoprotection by the nutrients. This includes, in addition to antioxidants, novel studies of omega-3 polyunsaturated fatty acids and nicotinamide.

Up-Regulated Expression of ICAM1, MT1A, PTGS2, LCE3D, PPARD, and GM-CSF2 Following Solar Skincare Protection and Repair Strategies in a 3-Dimensional Reconstructed Human Skin Model.

Background: Clinical, optical and histological research confirms that solar skin damage continues to pose a threat to human skin health globally despite widespread sunscreen usage and sun awareness campaigns. Despite this, very few studies examine the critical changes in gene expression and DNA repair activity following recommended topical solar protection and repair strategies to ameliorate the harmful effects of ultraviolet, visible light and near-infrared radiation. Purpose: To investigate alterations in gene expression following topical solar protection and solar repair strategies. Methods: Using epidermal keratinocytes and dermal fibroblasts derived from a 3-dimensional reconstructed human skin model, gene expression was assessed via the Genemarkers Standard Skin Panel using 112 genes deploying two analytical techniques: DNA microarray and quantitative real-time PCR exploration. Tissues were inoculated with products then collected after 24 hours following application of solar protection formulations and 16 hours following solar repair formulations (The Essential Six, RATIONALE, Victoria, Australia). Results: A DNA microarray revealed 67 genes that were significantly up-regulated or down-regulated following the treatment. The quantitative real-time PCR revealed that, in comparison to the control, the genes encoding Intercellular Adhesion Molecule 1 (ICAM1), Metallothionein 1A (MT1A), Prostaglandin-Endoperoxide Synthase 1 (PTGS2), Late Cornified Envelope 3D (LCE3D), Peroxisome Proliferator Activated Receptor (PPARD), and Granulocyte/Macrophage Colony Stimulating Factor 2 (GM-CSF2) have been up-regulated following usage of the solar protection regime, 1.87, 861.16, 4.34, 1.91, 1.06, and 3.6, respectively. ICAM1, MT1A, PTGS2, LCE3D, PPARD, and GM-CSF2 were up-regulated following use of the solar repair regime, 3.78, 2.98, 14.89, 5.09, 2.42, and 13.51, respectively. Conclusion: This study demonstrates that a specific solar protection and repair regime upregulated genes involved in photoprotection and repair mechanisms in a 3-dimensional (3D) reconstructed human-like skin model.

Biologically efficient solar radiation: Vitamin D production and induction of cutaneous malignant melanoma.

Solar ultraviolet (UV) radiation is the main source of vitamin D production and is also the most important environmental risk factor for cutaneous malignant melanoma (CMM) development. In the present study the relationships between daily or seasonal UV radiation doses and vitamin D status, dietary vitamin D intake and CMM incidence rates at different geographical latitudes were investigated. North-South gradients of 25-hydroxyvitamin D (25(OH)D) generation and CMM induction were calculated, based on known action spectra, and compared with measured vitamin D levels and incidence rates of CMM. The relative roles of UVA and UVB in CMM induction are discussed. Latitudinal dependencies of serum 25(OH)D levels and CMM incidence rates can only partly be explained by ambient UV doses. The UV sensitivity is different among populations with different skin color. This is well known for CMM, but seems also to be true for vitamin D status. The fact that UV-induced vitamin D may reduce the risk of CMM complicates the discussion. To some extent high dietary vitamin D intake seems to compensate low UV doses.