Mechanisms of Ultraviolet (UV) B and UVA Phototherapy

Ultraviolet (UV) radiation has been used for decades with great success and at a constantly increasing rate in the management of skin diseases, becoming an essential part of modern dermatologic therapy (Krutmann et al, 1999). For phototherapy, irradiation devices emitting either predominantly middlewave UV (UVB, 290-315 nm) or long-wave UV (UVA, 315-400 nm) radiation are employed. In former years, patients were treated with broad-band UVB, broad-band UVA, or combination regimens. Broad-band UV phototherapy, however, is being replaced more frequently by the use of irradiation devices that allow treatment of patients' skin with selected emission spectra. Two such modalities which have their origin in European Photodermatology are 311 nm UVB phototherapy (which uses long-wave UVB radiation above 300 nm rather than broadband UVB) and high-dose UVA1 therapy (which selective employs long-wave UVA radiation above 340 nm). In Europe, 311 nm UVB phototherapy has almost replaced classical broad-band UVB phototherapy and has significantly improved therapeutic efficacy and safety of UVB phototherapy (van Welden et al, 1988; Krutmann et al, 1999). The constantly increasing use of UVA-1 phototherapy has not only improved UVA phototherapy for established indications such as atopic dermatitis (Krutmann et al, 1992a, 1998; Krutmann, 1996), but has also provided dermatologists with the opportunity to successfully treat previously untractable skin diseases, e.g., connective tissue diseases (Stege et al, 1997; Krutmann, 1997).These clinical developments have stimulated studies about the mechanisms by which UVB and UVA phototherapy work. The knowledge obtained from this work is an indispensable prerequisite to make treatment decisions on a rationale rather than an empirical basis. Modern dermatologic phototherapy has started to profit from this knowledge, and it is very likely that this development will continue and provide dermatologists with improved phototherapeutic modalities and regimens for established and new indications. This review aims to provide an overview about current concepts of the mode of action of dermatologic phototherapy. Special emphasis will be given on studies that have identified previously unrecognized immunosuppressive/anti-inflammatory principles of UV phototherapy

Infrared A Radiation Influences the Skin Fibroblast Transcriptome: Mechanisms and Consequences

Infrared A (IRA) radiation (760–1440nm) is a major component of solar radiation and, similar to UVR, causes photoaging of human skin by increasing the expression of matrix metalloproteinase-1 in human skin fibroblasts. In this study, we assessed the IRA-induced transcriptome in primary human skin fibroblasts. Microarray analysis revealed 599 IRA-regulated transcripts. The IRA-induced transcriptome differed from changes known to be induced by UV. IRA-responsive genes include the categories extracellular matrix, calcium homeostasis, stress signaling, and apoptosis. Selected results were confirmed by real-time PCR experiments analyzing 13 genes representing these four categories. By means of chemical inhibitors of known signaling pathways, we showed that ERK1/2, the p38-, JNK-, PI3K/AKT-, STAT3-, and IL-6 as well as the calcium-mediated signaling pathways, are functionally involved in the IRA gene response and that a major part of it is triggered by mitochondrial and, to a lesser extent, non-mitochondrial production of reactive oxygen species. Our results identify IRA as an environmental factor with relevance for skin homeostasis and photoaging

Post-Transcriptional Regulation of Interleukin-6 Gene Expression in Human Keratinocytes by Ultraviolet B Radiation

Exposure to increasing doses (290-315 nm) of ultraviolet (UV) B radiation is thought to profoundly affect human health. Studies on the biologic and molecular effects of UVB radiation on human skin are therefore of particular interest. There is experimental and clinical evidence to assume that UVB radiation-induced local and systemic inflammatory reactions might be mediated at least in part by UVB-induced keratinocyte-derived interleukin (IL)-6. Previously, a UVB-induced increase of steady-state levels of IL-6 mRNA was found to be a prerequisite for keratinocyte IL-6 production after UVB irradiation. The present study was aimed at addressing the question of whether in vitro UVB irradiation would increase IL-6 mRNA expression in long-term cultured, normal human keratinocytes via transcriptional or post-transcriptional mechanisms. UVB exposure (0-100 J/m2) of keratinocytes increased low baseline expression levels of lL-6 mRNA in a time- and dose-dependent manner. Using nuclear run-on assays, transcription rates of the II,-6 gene in nuclei isolated from UVB-irradiated cells were found to be essentially identical to those seen in unirradiated cells, indicating that UVB light did not lead to increased transcription of the IL-6 gene. To determine a possible post-transcriptional mechanism in UVB-induced IL-6 mRNA expression, the effects of UVB irradiation on IL-6 mRNA stability were examined. To this end irradiated and unirradiated keratinocytes were treated with actinomycin D and subjected to Northern blot analysis to calculate IL-6 mRNA half-life. As compared with unirradiated cells, IL-6 mRNA stability was increased significantly (three- to four-fold) in UVB-irradiated cells, suggesting that UVB radiation upregulates IL-6 mRNA levels in human keratinocytes by increasing the stability of IL-6 transcripts. This is the first report indicating that UVB radiation at a physiologically relevant dose may affect gene expression in human cells at a post-transcriptional level

Laser Scanning Microscopic Investigations of the Decontamination of Soot Nanoparticles from the Skin

Background/Aims: Airborne pollutants, such as nano-sized soot particles, are increasingly being released into the environment as a result of growing population densities and industrialization. They can absorb organic and metal compounds with potential biological activity, such as polycyclic aromatic hydrocarbons and airborne pollen allergens. Local and systemic toxicities may be induced in the skin if the particulates release their harmful components upon dermal contact. Methods: In the present study, skin pretreatments with serum and/or shield as barrier formulations prior to exposure and washing with a cleanser subsequent to exposure were evaluated as a protection and decontamination strategy using laser scanning microscopy. Results: The results indicate that while the application of serum and a cleanser was insufficient for decontamination, the pretreatment with shield prior to nanoparticle exposure followed by washing led to the removal of a considerable amount of the carbon black particles. The combined application of serum and shield before the administration of carbon black particles and subsequent washing led to their elimination from the skin samples. Conclusion: The application of barrier-enhancing formulations in combination with a cleanser may reduce the penetration of harmful airborne particulates by preventing their adhesion to the skin and facilitating their removal by subsequent washing with the cleanser

Interleukin-10 Production by Cultured Human Keratinocytes: Regulation by Ultraviolet B and Ultraviolet A1 Radiation

Keratinocytes are the primary cellular target for ultraviolet radiation in human skin, and ultraviolet radiation-induced therapeutical effects may thus be mediated by keratinocyte-derived, antiinflammatory mediators. Interleukin-10 is capable of exerting anti-inflammatory effects by virtue of its capacity to suppress the production of interferon-γ. The present study therefore assessed the ability of cultured human keratinocytes to produce interleukin-10 following ultraviolet irradiation. Exposure of long-term cultured normal human keratinocytes to ultraviolet B(280-320 nm) or to ultraviolet A1 (340-400 nm) radiation caused a time- and dose-dependent induction of interleukin-10 mRNA expression and interleukin-10 protein secretion, with ultraviolet A1 radiation being the strongest stimulus. Ultraviolet radiation-induced interleukin-10 production by normal human keratinocytes was enhanced by a factor of two, when cells were cultured in high- rather than low-calcium medium. Neither addition of the ultraviolet radiation-inducible cytokines tumor necrosis factor-α or interleukin-1α to unirradiated keratinocytes nor presence of their respective neutralizing antibodies in cultures of irradiated keratinocytes induced or inhibited interleukin-10 synthesis. Modulation of eicosanoid production by addition of prostaglandin E2 to keratinocyte cultures or disturbance of cyclooxygenase activity by indomethacin did not affect interleukin-10 production in resting or irradiated cells. These studies demonstrate that cultured human keratinocytes are capable of producing interleukin-10. Human keratinocyte interleukin-10 production is dependent on the differentiation state of the cell and induced by ultraviolet B and, in particular, ultraviolet A1 radiation exposure. This novel property of ultraviolet radiation may account at least in part for the efficacy of phototherapy in inflammatory skin diseases