UVB Irradiation (uvb + irradiation)

Distribution by Scientific Domains


Selected Abstracts


Effect of UVA or UVB Irradiation on Cutaneous Lipids in Films or in Solution

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2010
Chloé Merle
The barrier function of the skin is largely due to the stratum corneum which is essentially composed of lipids. Different external factors, such as UV irradiation, affect this skin layer and are responsible for a destabilization of the supramolecular organization of its constituted lipids. In this work, mass spectrometry and infrared spectroscopy are combined to study the correlation between the formation of oxidative compounds by UV irradiation and the lipid organization. Experiments were carried out on unsaturated lipids in film or solution form, exposed to UVA or UVB irradiation. UV exposure leads to the formation of oxygenated entities in the case of lipids with an unsaturated fatty acid moiety, resulting in a decrease in their packing which is greater when the lipids are in solution. The packing decrease is even greater following UVB irradiation. [source]


UVB Irradiation of Normal Human Skin Favors the Development of Type-2 T-cells In Vivo and in Primary Dermal Cell Cultures,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2002
Sergio Di Nuzzo
ABSTRACT To determine the effect of UVB exposure on the balance of type-1 or type-2 T-cells in skin, we examined the expression of key markers interferon (IFN)-, and interleukin (IL)-4 in cryostat sections. IFN-, mRNA was clearly detectable in nonirradiated control skin, and IFN-, protein was found in 2% of the dermal CD3pos T-cells, whereas IL-4 mRNA was hardly detectable, and no IL-4 protein was found. In contrast, IL-4 mRNA expression increased upon irradiation, and IL-4 was found in 2% of the T-cells at day 2 after UVB-exposure. Concomitantly, IFN-, mRNA expression decreased, and IFN-, protein became absent. We also analyzed T-cells present in primary dermal cell cultures, which were used as an in vitro equivalent of the in vivo situation. As compared with T-cells from control skin, T-cells in dermal cell cultures from UVB-exposed skin displayed an increased IL-4 and decreased IFN-, expression. No such skewing occurred when the T-cells from irradiated skin were cloned in the absence of a dermal microenvironment. Except for an occasional positive T-cell, type-1,associated cell-surface markers (CCR5, CXCR3) or type-2 markers (CCR3, CD30, CRTH2) were undetectable in situ. But these markers were expressed on cultured dermal T-cells from UVB-exposed and control skin at a comparable level, but did not correlate with the IFN-, and IL-4 production. Altogether, UVB-induced changes of the dermal microenvironment favor the development of type-2 T-cells. [source]


Topically Applied Eicosapentaenoic Acid Protects Against Local Immunosuppression Induced by UVB Irradiation, cis -Urocanic Acid and Thymidine Dinucleotides,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2001
Ralf M. W. Moison
ABSTRACT UVB-induced immunosuppression, a promoter of photocarcinogenesis, involves the formation of pyrimidine dimers and cis -urocanic acid (cis -UCA), but reactive oxygen species (ROS) also plays an important role. Eicosapentaenoic acid (EPA) can inhibit photocarcinogenesis, but due to its polyunsaturated nature it is susceptible to oxidative damage by ROS. The antioxidant defense system may therefore be challenged upon ultraviolet-B (UVB) irradiation in the presence of EPA. We investigated whether topically applied EPA in mice could protect against local immunosuppression (contact hypersensitivity response to dinitrofluorobenzene) induced by UVB radiation (1.5 J/cm2), or topically applied cis -UCA (150 nmol/cm2) or thymidine dinucleotides (pTpT) (5 nmol/cm2). The influence of EPA on epidermal lipid peroxidation and antioxidant status was also measured. UVB irradiation, cis -UCA and pTpT all caused 70% immunosuppression. Topical pretreatment of mice with EPA partially protected against immunosuppression; the EPA dose needed to accomplish this was 10 nmol/cm2 for UVB irradiation, 100 nmol/cm2 for cis -UCA and 1000 nmol/cm2 for pTpT. Higher EPA doses caused higher UVB-induced lipid peroxidation and lower vitamin C levels. Glutathione only decreased with the highest EPA dose whereas vitamin E was not decreased after UVB irradiation. In conclusion, topically applied EPA protects against UVB-, cis -UCA- and pTpT-induced immunosuppression and maintenance of an adequate antioxidant defense seems to be an important prerequisite for the protective action by EPA. [source]


Mutation spectrum in UVB-exposed skin epidermis of Xpa -knockout mice: Frequent recovery of triplet mutations

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2007
Hironobu Ikehata
Abstract Knockout mutations in both alleles of the Xpa gene give rise to a complete deficiency in nucleotide excision repair (NER) in mammalian cells. We used transgenic mice harboring the ,-phage-based lacZ mutational reporter gene to study the effect of Xpa null mutation (Xpa,/,) on damage induction, repair, and mutagenesis in mouse skin epidermis after UVB irradiation. UVB induced equal amounts of cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (64PPs) in mouse skin epidermis of Xpa,/, and wild-type mice. Neither photolesion was removed in the Xpa,/, epidermis by 12 hr after irradiation whereas removal of 64PPs was observed in the epidermis of wild-type mice. Irradiation with 200 and 300 J/m2 UVB increased the lacZ mutant frequency in the epidermis of Xpa,/, mice, but the induced mutant frequencies were not significantly different from those previously determined for wild-type mice. One-hundred lacZ mutants isolated from the UVB-exposed epidermis of Xpa,/, mice were analyzed and compared with mutant sequences previously determined for irradiated wild-type mice. The distribution of the mutations along the lacZ transgene and the preferred dipyrimidine context of the UV-specific mutations were similar in mutants from the Xpa,/, and wild-type mice. The spectra of the mutations in the two genotypes were both highly UV-specific and similar in a dominance of C , T transitions at dipyrimidine sites; however, Xpa,/, mice had a higher frequency than wild-type mice of two-base tandem substitutions, including CC , TT mutations, three-base tandem mutations and double base substitutions that were separated by one unchanged base in a three-base sequence (alternating mutations). These tandem/alternating mutations included a remarkably large number of triplet mutations, a recently reported, novel type of UV-specific mutation, characterized by multiple base substitutions or frameshifts within a three-nucleotide sequence containing a dipyrimidine. We conclude that the triplet mutation is a UV-specific mutation that preferably occurs in NER-deficient genetic backgrounds. Environ. Mol. Mutagen., 2007. © 2006 Wiley-Liss, Inc. [source]


Selective down-regulation of the ,6-integrin subunit in melanocytes by UVB light

EXPERIMENTAL DERMATOLOGY, Issue 6 2005
Sven Krengel
Abstract:,In vivo, melanocytes bind to laminin (LM) molecules of the basement membrane (BM) via the integrins ,3,1 and ,6,1, and they adhere to neighbouring keratinocytes via E-cadherin. Only few studies have addressed the impact of ultraviolet (UV) light on the interaction of melanocytes with their microenvironment. In this report, we examined the influence of UVB irradiation on the expression of the most important melanocyte-adhesion molecules (E-, N-cadherin, ,2-, ,3-, ,5-, ,6-, ,V-, ,1-, ,3-integrins and ICAM-1) in vitro by flow cytometry. We were able to demonstrate that the ,6-integrin subunit is selectively and reversibly down-regulated by UVB in a dwzm 150ose-dependent manner. In comparison, keratinocytes lacked UVB-inducible alterations in the expression of ,6-integrin. In the presence of LM-1, the UVB-induced down-regulation of ,6-integrin in melanocytes was significantly reduced. Moreover, LM-1 increased the resistance of melanocytes to UVB-induced cell death, as measured by annexinV-binding analysis. This effect was reversed by preincubation with an ,6-integrin-blocking antibody. By immunofluorescence, we could demonstrate that UVB leads to a dose-dependent internalization of ,6-integrin, providing an obvious explanation for the down-regulation on the outer cell surface observed by flow cytometry. We suggest that adhesion to LM-1 through ,6-integrin represents a protective mechanism for melanocytes to withstand UVB damage. Through ,6-integrin internalization, sunburns might alter the interaction between melanocytes and the BM, resulting in apoptosis induced by loss of anchorage (anoikis). Repeated sunburns may then lead to the selection of a population of melanocytes which are capable of anchorage-independent survival, culminating in solar nevogenesis and melanoma development. [source]


In vivo UVB irradiation induces clustering of Fas (CD95) on human epidermal cells

EXPERIMENTAL DERMATOLOGY, Issue 6 2003
Bo Bang
Abstract:,In vitro studies with human cell lines have demonstrated that the death receptor Fas plays a role in ultraviolet (UV)-induced apoptosis. The purpose of the present study was to investigate the relation between Fas expression and apoptosis as well as clustering of Fas in human epidermis after a single dose of UVB irradiation. Normal healthy individuals were irradiated with three minimal erythema doses (MED) of UVB on forearm or buttock skin. Suction blisters from unirradiated and irradiated skin were raised, and Fas, FasL, and apoptosis of epidermal cells were quantified by flow cytometry. Clustering of Fas was demonstrated by confocal laser scanning microscopy on cryostat sections from skin biopsies. Soluble FasL in suction blister fluid was quantified by ELISA. Flow cytometric analysis demonstrated increased expression intensity of Fas after irradiation, with 1.6-, 2.2- and 2.7-fold increased median expression at 24, 48 and 72 h after irradiation, respectively (n = 4). Apoptosis was demonstrated by the TUNEL reaction, and the maximum of apoptotic cells was detected at 48 h after irradiation. Double-staining for Fas and TUNEL showed that apoptosis was restricted to the Fas-positive epidermal subpopulation, but there was no correlation between the intensities of Fas expression and TUNEL reaction. Median expression intensity of FasL-positive cells transiently decreased to 0.9- and 0.8-fold of the preirradiation respective level after 24 h and 48 h, respectively, and returned to the respective preirradiation level at 72 h after irradiation (n = 4). Concentrations of soluble FasL in suction blister fluid from UVB-irradiated skin did not differ from those in unirradiated skin (n = 5). Confocal laser scanning microscopy showed a rapid clustering of Fas within 30 min after irradiation. A simultaneous clustering of the adapter signalling protein FADD suggested that Fas clustering has a functional significance. Our results are in accordance with previous findings from in vitro studies, and suggest that Fas is activated in vivo in human epidermis after UVB exposure. [source]


The effect of ultraviolet B irradiation on nitric oxide synthase expression in murine keratinocytes

EXPERIMENTAL DERMATOLOGY, Issue 6 2000
M. Sasaki
Abstract: Nitric oxide (NO), which has several physiological functions in skin, is generated by NO synthase (NOS). NOS has at least three isoforms; endothelial NOS (eNOS), brain NOS (bNOS), and inducible NOS (iNOS). Ultraviolet B (UVB) irradiation has been reported to stimulate NO production in skin via induction or activation of NOS, however, the exact mechanism of NOS induction by UVB irradiation remains obscure. In this study, we investigated the direct effect of UVB on the expression of NOS isoforms in murine keratinocytes, and found a significant increase in NO production within 48 h. mRNA and protein expressions of bNOS were both enhanced by UVB irradiation in murine keratinocytes, whereas iNOS mRNA expression was suppressed at 4 and 12 h after UVB irradiation. These results suggest that the enhancement of NO production observed after UVB irradiation in murine keratinocytes may be explained in part by the upregulation of bNOS expression, but not iNOS expression. [source]


Photochemical cleavage of a tattoo pigment by UVB radiation or natural sunlight

JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 7 2007
Eva Engel
Summary Background: Millions of people have at least one tattoo. Complex and light absorbing molecules are implanted in the skin. When tattooed skin receives UV radiation or natural sunlight, photochemical cleavage of the pigments may occur. As a first step, we dissolved pigments in a suitable solvent and analyzed them after light irradiation. Methods: The widespread Pigment Red 22 was dissolved in different solvents. The solutions were irradiated with either UVB radiation (up to 8 h) or with natural sunlight (110 days). After irradiation, the solutions were analyzed by means of liquid chromatography and mass spectrometry. Results: A clear cleavage of the pigment was detected in all solvents and the primary decomposition products were identified. In tetrahydrofuran and dioxane, the pigment concentration decreased significantly during UVB irradiation, whereas the pigment was completely destroyed during sunlight exposure. In chloroform and dichloromethane, the pigment concentration decreased slightly during UVB irradiation, whereas the pigment was almost completely destroyed during sunlight exposure. Conclusion: Since chloroform and dichloromethane do not affect the cleavage process, these solvents are optimal for such in vitro experiments. We have shown the cleavage of the tattoo pigment Red 22 when exposed to UVB radiation or natural sunlight. The decomposition products are hazardous showing a potential risk of being toxic or even carcinogenic. At present, a risk assessment is not feasible since the concentration of pigments and their decomposition products in skin are unknown. [source]


Cadherin expression pattern in melanocytic tumors more likely depends on the melanocyte environment than on tumor cell progression

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2004
Sven Krengel
Background:, Adhesion molecules have been assigned an important role in melanocytic tumor progression. By the loss of E-cadherin, melanocytes might escape the control of neighbouring keratinocytes. Although in vitro data support this hypothesis, there are yet no conclusive immunohistochemical results on cadherin expression in melanocytic tumors. Objective:, To gain detailed insight in the expression of cadherins and their cytoplasmic binding partners, the catenins, in various types of benign and malignant melanocytic neoplasms. Methods:, Immunohistochemical analysis of the expression of E-, P-, and N-cadherin and ,-, ,-, and ,-catenin in compound and dermal nevi, Spitz nevi, blue nevi, ultraviolet B (UVB)-irradiated nevi, and malignant melanomas of various tumor thickness. Results:, In both nevi and melanomas, E-cadherin expression in melanocytic cells decreased, following a gradient from junctional to deeper dermal localization. The pattern of E-cadherin expression was more heterogeneous in melanomas than in nevi. In some melanomas, E-cadherin was only weakly positive in the epidermal tumor cells. P-cadherin expression was similar to that of E-cadherin. N-cadherin expression in melanocytic lesions was a rare finding, however, a small percentage of melanomas showed expression in some cell nests. Some Spitz nevi exhibited strong N-cadherin immunoreactivity. Most melanocytic cells were ,- and ,-catenin-positive and ,-catenin-negative. UVB irradiation did not influence the expression of cadherins and catenins in melanocytic nevi in vivo. Conclusions:, It is presumed that the gradual loss of E-cadherin expression represents a reaction of melanocytic cells to altered conditions in the dermal environment, e.g. lack of contact to keratinocytes, or new contact with dermal extracellular matrix molecules, respectively. Melanoma cells apparently are less dependent on these environmental factors and, therefore, show a more heterogeneous expression pattern. This might be of importance for the adaptation of the tumor cells to local requirements. However, in view of our results, a causative role of (loss of ) E-cadherin or (gain of ) N-cadherin for melanocytic tumor progression still remains to be proven. [source]


Effects of repeated low-dose UVB irradiation on the hyphal growth of Candida albicans

MYCOSES, Issue 1 2006
J. Brasch
Summary Ultraviolet B light (UVB) can have negative phototropic effects on fungi. Candida albicans is often found on human skin exposed to UVB. Therefore, it is of medical interest to know whether a negative phototropic response to UVB irradiation can support an invasive growth of this potentially dangerous agent. In our study we investigated how repeated irradiation with low doses of UVB can influence the hyphal growth of C. albicans. Six randomly chosen strains of C. albicans were tested. Formation of hyphae was induced and maintained within transparent agar plates. The fungi were exposed to UVB three times daily for 7 days from either the obverse or the reverse side during incubation. The wavelength spectrum was in the range of 310,315 nm, single doses were between 0.0018 and 0.432 J cm,2. After 7 days the morphology and growth direction of C. albicans cells were determined microscopically. All six strains showed a common and dose-dependent response to UVB irradiation: the progression of hyphal growth was inhibited, no phototropic effects were seen and as a new finding an increased formation of blastospores was observed. We conclude that an irradiation of human skin colonized by C. albicans with doses of UVB that can occur under natural or artificial conditions is unlikely to trigger skin invasion by C. albicans. [source]


Ultraviolet B Radiation of Human Skin Generates Platelet-activating Factor Receptor Agonists

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2010
Jared B. Travers
Ultraviolet B radiation (UVB) is a potent stimulator of epidermal cytokine production. In addition to cytokines, such as tumor necrosis factor-alpha (TNF-,), UVB generates bioactive lipids including platelet-activating factor (PAF). Our previous in vitro studies in keratinocytes or epithelial cell lines have demonstrated that UVB-mediated production of PAF agonists is due primarily to the pro-oxidative effects of this stimulant, resulting in the nonenzymatic production of modified phosphocholines (oxidized glycerophosphocholines). The current studies use human skin to assess whether UVB irradiation generates PAF-receptor agonists, and the role of oxidative stress in their production. These studies demonstrate that UVB irradiation of human skin results in PAF agonists, which are blocked by the antioxidant vitamin C and the epidermal growth factor receptor inhibitor PD168393. Inasmuch as UVB-generated PAF agonists have been implicated in animal model systems as being involved in photobiologic processes including systemic immunosuppression and cytokine (TNF-,) production, these studies indicate that this novel activity could be involved in human disease. [source]


French Maritime Pine Bark (Pinus maritima Lam.) Extract (Flavangenol®) Prevents Chronic UVB Radiation-induced Skin Damage and Carcinogenesis in Melanin-possessing Hairless Mice

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2010
Yoshiyuki Kimura
A French maritime pine bark extract, Flavangenol®, is widely used as a nutritional supplement for protection against atherosclerosis, hypertension, diabetes, etc. Chronic exposure to solar UV radiation damages skin, increasing cutaneous thickness, wrinkling and pigmentation, as well as reducing elasticity, and causes skin cancer. The aim of this study was to examine the effects of flavangenol on skin damage and the incidence of skin tumors caused by long-term UVB irradiation in melanin-possessing hairless mice. The oral administration of flavangenol (60, 200 or 600 mg kg,1, twice daily) significantly inhibited increases in skin thickness, and the formation of wrinkles and melanin granules, as well as increases in the diameter and length of skin blood vessels. Furthermore, it prevented increases in numbers of apoptotic, Ki-67-positive and 8-hydroxy-2,-deoxyguanosine (8-OHdG)-positive cells, and the expression of skin vascular endothelial growth factor (VEGF) induced by chronic UVB irradiation. The effect on these biomarkers was associated with a reduction in the incidence of tumors in mice. The antiphotoaging and anticarcinogenetic activities of flavangenol may be due to inhibition of the expression of Ki-67, 8-OHdG and VEGF through a scavenging effect on reactive oxygen species. [source]


Effect of UVA or UVB Irradiation on Cutaneous Lipids in Films or in Solution

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2010
Chloé Merle
The barrier function of the skin is largely due to the stratum corneum which is essentially composed of lipids. Different external factors, such as UV irradiation, affect this skin layer and are responsible for a destabilization of the supramolecular organization of its constituted lipids. In this work, mass spectrometry and infrared spectroscopy are combined to study the correlation between the formation of oxidative compounds by UV irradiation and the lipid organization. Experiments were carried out on unsaturated lipids in film or solution form, exposed to UVA or UVB irradiation. UV exposure leads to the formation of oxygenated entities in the case of lipids with an unsaturated fatty acid moiety, resulting in a decrease in their packing which is greater when the lipids are in solution. The packing decrease is even greater following UVB irradiation. [source]


Requirement for Metalloproteinase-dependent ERK and AKT Activation in UVB-induced G1-S Cell Cycle Progression of Human Keratinocytes

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2009
Weinong Han
UVB (280,315 nm) in natural sunlight represents a major environmental challenge to the skin and is clearly associated with human skin cancer. Here we demonstrate that low doses of UVB induce keratinocyte proliferation and cell cycle progression of human HaCaT keratinocytes. Different from UVA, UVB irradiation induced extracellular signal-regulated kinase (ERK) and AKT activation and their activation are both required for UVB-induced cell cycle progression. Activation of epidermal growth factor receptor (EGFR) was observed after UVB exposure and is upstream of ERK/AKT/cyclin D1 pathway activation and cell cycle progression following UVB radiation. Furthermore, metalloproteinase (MP) inhibitor GM6001 blocked UVB-induced ERK and AKT activation, cell cycle progression, and decreased the EGFR phosphorylation, demonstrating that MPs mediate the EGFR/ERK/AKT/cyclin D1 pathways and cell cycle progression induced by UVB radiation. In addition, ERK or AKT activation is essential for EGFR activation because ERK or AKT inhibitor blocks EGFR activation following UVB radiation, indicating that EGFR/AKT/ERK pathways form a regulatory loop and converge into cell cycle progression following UVB radiation. Identification of these signaling pathways in UVB-induced cell cycle progression of quiescent keratinocytes as a process mimicking tumor promotion in vivo will facilitate the development of efficient and safe chemopreventive and therapeutic strategies for skin cancer. [source]


Akt1-mediated Intracellular Oxidation after UVB Irradiation Suppresses Apoptotic Cell Death Induced by Cell Detachment and Serum Starvation

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2008
Yuko Ibuki
Apoptosis is an important cell death system that deletes damaged and mutated cells to prevent cancer. We have previously reported that a certain dose of UVB irradiation inhibited the apoptosis induced by serum starvation and cell detachment, leading to cell transformation. This antiapoptotic effect was partially inhibited by phosphatidylinositol 3-kinase (PI3-kinase) inhibitors. UVB irradiation is known to cause the phosphorylation of Akt via the activation of PI3-kinase; however, the Akt isoform-specific relationship has not yet been clarified. Notably, the role in antiapoptotic effect of UVB has yet to be elucidated. In this study, the role of Akt1 in the UVB-induced inhibition of apoptosis was examined by Akt1 knockdown using small interfering RNA (siRNA). NIH3T3 cells showed typical apoptotic cell death by serum starvation and cell detachment, which was significantly inhibited by UVB irradiation. Akt1 knockdown decreased the antiapoptotic effect of UVB. Hydrogen peroxide-induced suppression of cell death was also decreased in Akt1 knockdown cells. An antioxidant, N -acetylcysteine, inhibited the antiapoptotic effect by UVB irradiation, whereas no inhibition was observed in Akt1 knockdown cells. Furthermore, UVB-induced intracellular peroxidation was not observed in the knockdown cells, indicating that Akt1 played an important role in mediating the intracellular redox status. Treatment with insulin had a similar antiapoptotic effect as UVB irradiation involving intracellular peroxidation, which was also attenuated in Akt1 knockdown cells. These findings suggest that appropriate intracellular oxidation after UVB irradiation prevented apoptosis, a process which might be partially regulated by the production of reactive oxygen species mediated by Akt1. [source]


Decrease in Langerhans Cells and Increase in Lymph Node Dendritic Cells Following Chronic Exposure of Mice to Suberythemal Doses of Solar Simulated Radiation

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 5 2005
Pauline McLoone
ABSTRACT Exposure of certain strains of mice to ultraviolet radiation (UVR) causes suppression of some innate and adaptive immune responses. One such consequence of acute UVB exposure is a reduction in the number of Langerhans cells (LC) in the epidermis and an increase in dendritic cells (DC) in lymph nodes draining the irradiated skin sites. Exposure to chronic UVB irradiation also has effects on the immune system, but it is unknown what effects are caused by repeated doses of solar simulated radiation (SSR). Consequently, the main aims of the present study were to determine whether repeated exposure to low doses of SSR would lead to similar changes in these cell populations and whether chronic doses of SSR activate a protective photoadaptation mechanism. Groups of C3H/HeN mice were irradiated daily with 3.7 J/cm2 SSR from Cleo Natural lamps for 2, 10, 20, 30 or 60 days. Further groups of mice received an additional dose of 7.4 J/cm2 SSR on days 2, 10, 30 or 60 to test for photoadaptation. The numbers of LC in the epidermis and DC in the lymph nodes draining irradiated skin sites were counted 24 h after the final irradiation. With the exception of mice irradiated for only 2 days, LC were significantly reduced throughout the chronic irradiation protocol, and no recovery occurred. DC numbers were significantly increased in the draining lymph nodes of mice irradiated for 20 days and 60 days. [source]


Photoreactivation in Paramecium tetraurelia under Conditions of Various Degrees of Ozone Layer Depletion,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2005
Akihisa Takahashi
ABSTRACT Photoreactivation (PR) is an efficient survival mechanism that helps protect cells against the harmful effects of solar-ultraviolet (UV) radiation. The PR mechanism involves photolyase, just one enzyme, and can repair DNA damage, such as cyclobutane-pyrimidine dimers (CPD) induced by near-UV/blue light, a component of sunlight. Although the balance of near-UV/blue light and far-UV light reaching the Earth's surface could be altered by the atmospheric ozone layer's depletion, experiments simulating this environmental change and its possible effects on life have not yet been performed. To quantify the strength of UVB in sunlight reaching the Earth's surface, we measured the number of CPD generated in plasmid DNA after UVB irradiation or exposure to sunlight. To simulate the increase of solar-UV radiation resulting from the ozone layer depletion, Paramecium tetraurelia was exposed to UVB and/or sunlight in clear summer weather. PR recovery after exposure to sunlight was complete at a low dose rate of 0.2 J/m2·s, but was less efficient when the dose rate was increased by a factor of 2.5 to 0.5 J/m2·s. It is suggested that solar-UV radiation would not influence the cell growth of P. tetraurelia for the reason of high PR activity even when the ozone concentration was decreased 30% from the present levels. [source]


Cyclooxygenase-2 Expression in Murine and Human Nonmelanoma Skin Cancers: Implications for Therapeutic Approaches,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2002
Kathy P. An
ABSTRACT Inflammatory stimuli result in the production of cutaneous eicosanoids, which are known to contribute to the process of tumor promotion. Cyclooxygenase (COX), the rate-limiting enzyme for the production of prostaglandins (PG) from arachidonic acid, exists in at least two isoforms, COX-1 and COX-2. COX-1 is constitutively expressed in most tissues and plays various physiological roles, whereas increased COX-2 expression is known to occur in several types of epithelial neoplasms. Enhanced PG synthesis is a potential contributing factor in UVB-induced nonmelanoma skin cancers (NMSC). Increased COX-2 staining occurs in murine skin neoplasms after chronic exposure to carcinogenic doses of UVB. In this study, immunohistochemical and Western blot analyses were employed to assess longitudinally COX-2 expression in a standard mouse UVB complete carcinogenesis protocol and in human basal cell carcinomas (BCC) and squamous cell carcinomas (SCC). During UVB irradiation of mice, COX-2 expression consistently increased in the hyperplastic skin, the benign papillomas and the SCC. COX-2 expression was also increased in human actinic keratoses, SCC and BCC as well as in murine SCC and BCC. The pattern of COX-2 expression was quite variable, occurring in a patchy distribution in some lesions with staining confined mainly to suprabasal cell layers. In general, COX-2 expression progressively became more extensive in benign papillomas and well-differentiated murine SCC. The staining was predominantly cytoplasmic and perinuclear in some focal areas in tissue stroma around both murine and human tumors. Western blot analysis confirmed negative COX-2 expression in normal skin, whereas acute UVB exposure resulted in increased enzyme expression, which continued to increase in developing papillomas and SCC. Because of the evidence indicating a pathogenic role for eicosanoids in murine and human skin neoplasms, we performed studies to assess the anti-inflammatory and anticarcinogenic effects of green tea extracts, which are potent antioxidants. Acute exposure of the human skin to UVB (minimum erythema dose × 4) caused a transient enhancement of the COX-2 expression, which reverted to baseline within hours; however, in murine skin the expression persisted for several days. Pretreatment with the topically applied green tea extract (1 mg/cm2) largely abrogated the acute COX-2 response to UVB in mice or humans. In summary, enhanced COX-2 expression serves as a marker of epidermal UVB exposure for murine and human NMSC. These results suggest that COX-2 inhibitors could have potent anticarcinogenic effects in UVB-induced skin cancer. [source]


Activation of HIV in Human Skin by Ultraviolet B Radiation and its Inhibition by NF,B Blocking Agents,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2001
Joan Breuer-McHam
ABSTRACT To determine whether ultraviolet B (UVB) irradiation leads to activation of HIV in human skin, we conducted prospective and controlled studies in two academic medical centers in Texas from July 1995 to April 1999. HIV-positive patients with UV-treatable skin diseases were enrolled at each center, 18 subjects at one and 16 at the other. In one center, specimens from lesional and nonlesional skin biopsies were taken before and after sham- or UVB-irradiation administered in vivo or in vitro. In the other center, UVB phototherapy was administered three times weekly and specimens from skin biopsies were taken before and after 2 weeks (six treatments). Cutaneous HIV load was assessed using reverse transcriptase-polymerase chain reaction and reverse transcriptase-polymerase chain reaction in situ hybridization. UVB irradiation led to a 6,10-fold increase in the number of HIV in skin. To ascertain a role for nuclear factor kappa B (NF,B) in UVB-inducible HIV activation, two types of blockers, NF,B oligonucleotide decoy and sodium salicylate, were tested; each inhibited UVB-inducible HIV activation in skin partially. We conclude that UVB irradiation leads to increased numbers of HIV in human skin via processes that include release of cytoplasmic NF,B. [source]


In Vitro and In Vivo Transfer of bcl-2 Gene into Keratinocytes Suppresses UVB-induced Apoptosis,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2001
Hidetoshi Takahashi
ABSTRACT Bcl-2 is a member of the large Bcl-2 family and protects cells from apoptosis. Ultraviolet B (UVB) irradiation induces apoptosis of keratinocytes that is known as "sunburn cells." Previously we reported that UVB irradiation induces apoptosis accompanied by sequential activation of caspase 8, 3 and 1 in keratinocytes, and that the process is inhibited by various caspase inhibitors. Using bcl-2,expressing adenovirus vector we investigated the effect of Bcl-2 on UVB-induced apoptosis. Adenovirus vector efficiently introduced bcl-2 gene in cultured normal mouse keratinocytes (NMK cells); almost all NMK cells (1 × 106) were transfected at 1 × 108 plaque-forming unit (PFU)/mL. Bcl-2,transfected NMK cells were significantly resistant to UVB-induced apoptosis with the suppressive effect dependent on the Bcl-2 expression level. Following UVB irradiation caspase 8, 3 and 9 activities were stimulated in NMK cells, whereas in bcl-2,transfected cells only caspase 8, but not caspase 3 or 9, activity was stimulated. In order to investigate the effect of Bcl-2 in vivo topical application of Ad-bcl-2 on tape-stripped mouse skin was performed. Following the application Bcl-2 was efficiently overexpressed in almost all viable keratinocytes. The expression was transient with the maximal expression of Bcl-2 on the first day following the application of 1 × 109 PFU in 200 ,L. The introduced Bcl-2 remained at least for 6 days. UVB irradiation (1250 J/m2) induced apoptosis within 12 h and the maximal effect was observed at 24 h in control mouse skin. Both bcl-2,transfected and topical caspase 3 inhibitor-treated mice skin were resistant to UVB-induced apoptosis. The suppressive effect of Bcl-2 was more potent than that of caspase 3 inhibitor application. Topical application of empty adenovirus vector alone had no effect on Bcl-2 expression or UVB-induced apoptosis. These results indicate that adenovirus vector is an efficient gene delivery system into keratinocytes and that Bcl-2 is a potent inhibitor of UVB-induced apoptosis both in vitro and in vivo. [source]


Topically Applied Eicosapentaenoic Acid Protects Against Local Immunosuppression Induced by UVB Irradiation, cis -Urocanic Acid and Thymidine Dinucleotides,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2001
Ralf M. W. Moison
ABSTRACT UVB-induced immunosuppression, a promoter of photocarcinogenesis, involves the formation of pyrimidine dimers and cis -urocanic acid (cis -UCA), but reactive oxygen species (ROS) also plays an important role. Eicosapentaenoic acid (EPA) can inhibit photocarcinogenesis, but due to its polyunsaturated nature it is susceptible to oxidative damage by ROS. The antioxidant defense system may therefore be challenged upon ultraviolet-B (UVB) irradiation in the presence of EPA. We investigated whether topically applied EPA in mice could protect against local immunosuppression (contact hypersensitivity response to dinitrofluorobenzene) induced by UVB radiation (1.5 J/cm2), or topically applied cis -UCA (150 nmol/cm2) or thymidine dinucleotides (pTpT) (5 nmol/cm2). The influence of EPA on epidermal lipid peroxidation and antioxidant status was also measured. UVB irradiation, cis -UCA and pTpT all caused 70% immunosuppression. Topical pretreatment of mice with EPA partially protected against immunosuppression; the EPA dose needed to accomplish this was 10 nmol/cm2 for UVB irradiation, 100 nmol/cm2 for cis -UCA and 1000 nmol/cm2 for pTpT. Higher EPA doses caused higher UVB-induced lipid peroxidation and lower vitamin C levels. Glutathione only decreased with the highest EPA dose whereas vitamin E was not decreased after UVB irradiation. In conclusion, topically applied EPA protects against UVB-, cis -UCA- and pTpT-induced immunosuppression and maintenance of an adequate antioxidant defense seems to be an important prerequisite for the protective action by EPA. [source]


Evaluating the cytotoxic doses of narrowband and broadband UVB in human keratinocytes, melanocytes, and fibroblasts

PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 3 2008
Tae-Ho Cho
Summary Background: No comparative and simultaneous in vitro studies have been performed to determine the cytotoxic dose of narrowband UVB (NBUVB) and broadband UVB (BBUVB) for keratinocytes, melanocytes, and fibroblasts. Culture medium was often replaced with phosphate-buffered saline (PBS) before UV irradiation; however, its amount differed across studies. We determined the cytotoxic doses of NBUVB and BBUVB and tested for changes in viability according to the amount of PBS. Methods: We exposed cultured human keratinocytes, melanocytes, and fibroblasts to ultraviolet light in the range 12.5,1000 mJ/cm2 for NBUVB and 1.25,100 mJ/cm2 for BBUVB. The viability was assessed after 24 h. We also determined changes in viability at cytotoxic doses according to the amount of PBS (40, 80, and 120 ,l/well in a 96-well plate). Results: Cytotoxicity was observed at doses of 100, 200, and 400 mJ/cm2 for NBUVB and 5, 10, and 25 mJ/cm2 for BBUVB in keratinocytes, melanocytes, and fibroblasts, respectively. At cytotoxic doses, there was no change in viability according to the amount of PBS. Conclusions: Fibroblasts are more resistant to UVB irradiation, irrespective of the amount of NBUVB and BBUVB, than keratinocytes and melanocytes. The amount of PBS during irradiation had no effect on viability. [source]


Anti-wrinkling effects of the mixture of vitamin C, vitamin E, pycnogenol and evening primrose oil, and molecular mechanisms on hairless mouse skin caused by chronic ultraviolet B irradiation

PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 5 2007
Ho-Song Cho
Background: Naturally occurring antioxidants were used to regulate the skin damage caused by ultraviolet (UV) radiation because several antioxidants have demonstrated that they can inhibit wrinkle formation through prevention of matrix metalloproteinases (MMPs) and/or increase of collagen synthesis. Objective: We examined the effect of oral administration of the antioxidant mixture of vitamin C, vitamin E, pycnogenol, and evening primrose oil on UVB-induced wrinkle formation. In addition, we investigated the possible molecular mechanism of photoprotection against UVB through inhibition of collagen-degrading MMP activity or through enhancement of procollagen synthesis in mouse dorsal skin. Methods: Female SKH-1 hairless mice were orally administrated the antioxidant mixture (test group) or vehicle (control group) for 10 weeks with UVB irradiation three times a week. The intensity of irradiation was gradually increased from 30 to 180 mJ/cm2. Microtopographic and histological assessment of the dorsal skins was carried out at the end of 10 weeks to evaluate wrinkle formation. Western blot analysis and EMSA were also carried out to investigate the changes in the balance of collagen synthesis and collagen degradation. Results: Our antioxidant mixture significantly reduced UVB-induced wrinkle formation, accompanied by significant reduction of epidermal thickness, and UVB-induced hyperplasia, acanthosis, and hyperkeratosis. This antioxidant mixture significantly prevented the UVB-induced expressions of MMPs, mitogen-activated protein (MAP) kinase, and activation of activator protein (AP)-1 transcriptional factor in addition to enhanced type I procollagen and transforming growth factor-,2 (TGF-,2) expression. Conclusion: Oral administration of the antioxidant mixture significantly inhibited wrinkle formation caused by chronic UVB irradiation through significant inhibition of UVB-induced MMP activity accompanied by enhancement of collagen synthesis. [source]


Ultraviolet B radiation suppresses Langerhans cell migration in the dermis by down-regulation of ,4 integrin

PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 3 2006
Motoko Hamakawa
Background/Purpose: Ultraviolet B (UVB) radiation affects the migration and function of epidermal Langerhans cells (LC) and causes immunosuppression of contact hypersensitivity. It is known that LC leaves the epidermis after exposure to UVB. To know the behavior of LC in the dermis after UVB radiation, we studied the effect of UVB radiation on the expression of integrin families on freshly isolated or cultured murine LC. We also examined whether UVB radiation affects the migration of LC to secondary lymphoid tissue chemokine (SLC/6Ckine). Methods: Integrin expressions of murine LC cultured in epidermal cell suspension were analyzed using flowcytometry. We used murine LC sorted flowcytometrically for binding assay to extracellular matrix and for migration assay to chemokine. Skin explant assay and immnohistochemical staining for ,cords formation' were performed as previously described. Results: Twenty and 40 mJ/cm2 of UVB radiation down-regulated the expression of ,4 integrin on 24 h-cultured LC, but not that of ,6, ,1, or ,4 integrin. The number of cultured LC adhered to fibronectin, a ligand for ,4 integrin, was decreased after UVB irradiation, while that to laminin, a ligand for ,6 integrin, was not influenced. UVB radiation reduced the number of migrating LC to SLC. Furthermore, skin sheet explant experiments showed that UVB radiation inhibited the ,cords' formation in dermal vessels of the 48 h-cultured skin. Conclusions: These data suggest that UVB radiation may suppress the migration of LC from the dermis to lymphatic vessels. UVB radiation may downregulate the adherence of LC to dermal fibronectin and migration to SLC, and consequently suppress the migration of LC from the UVB-irradiated dermis to lymphatics. [source]


Gene expression profiles of TNF-,, TACE, furin, IL-1, and matrilysin in UVA- and UVB-irradiated HaCat cells

PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 4 2005
Beata Skiba
Background/Purpose: It is known that solar ultraviolet (UV) irradiation exerts multiple effects on mammalian skin tissues, one of which is the induction of local and systemic immunosuppression as well as inflammation. Tumor necrosis factor-, (TNF-,) and other cytokines are suggested to play a role in these responses. Quantitative real-time polymerase chain reaction (TaqMan RTPCR) was used to elucidate the effect of UVA and UVB irradiation on the expression of genes coding for TNF-,, IL-1,, IL-10, FasL, matrilysin, TACE and furin in HaCaT cells over a 48 h period (IL-1,, interleukin-1,; FasL, Fas ligand). Methods: Cultured HaCaT cells were either sham irradiated (control) or exposed to UVA (2000 and 8000 J/m2) or UVB (200 and 2000 J/m2) radiation. RNA was extracted from cells at 0, 4, 8, 12, 16, 24, 48 h post-irradiation and reverse transcribed to generate cDNA for subsequent real-time PCR amplification. Results: Significant increases in the mRNA levels for all genes tested were detected in both UVA- and UVB-irradiated HaCaT cells compared with control (sham-irradiated) cells. TNF-, mRNA levels were immediately up-regulated (0 h) after irradiation, with maximal induction at 8 h post 2000 J/m2 UVA and 200 J/m2 UVB irradiation, at 4 h post 8000 J UVA irradiation and at 48 h post 2000 J/m2 UVB irradiation. No correlation was observed between TNF-,, TACE and furin mRNA induction in the different irradiated cohorts. Conclusion: Results suggest that time-distinct gene induction of TNF-,, furin, IL-1, and matrilysin may be involved in UV-induced cellular responses, but not for TACE. In general, mRNA induction was dose dependent at some time points post-irradiation, but not throughout the whole time course tested. Our results show that quantitative real-time PCR is a useful tool in the analysis of quantitative changes of mRNA levels in cultured HaCaT cells after UV exposure. [source]


The effects of EGb 761 on lipid peroxide levels and superoxide dismutase activity in sunburn

PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 3 2002
Mehtap Kilinc Ozkur
Background/Purpose: Free oxygen radicals are involved in inflammatory skin reactions induced by ultraviolet B (UVB). In this study, the effect of a herbal antioxidant Ginkgo biloba extract (EGb 761) was investigated in UVB irradiated mice skin. Methods: The study was carried out on four groups of mice (n = 6 in each group). The first group was a control group (G1). The second group (G2) was only exposed to acute UVB irradiation. The third group (G3) received 100 mg/kg/day of EGb 761 orally for 5 days before UVB irradiation and the fourth group (G4) was given only a single dose of EGb 761 immediately after UVB irradiation. Eighteen hours after exposing to UVB, lipid peroxide levels, and superoxide dismutase (SOD) activities were studied and UVB damage was evaluated histopathologically according to ,sun-burn cell count'. Results: The SOD activities and Malondialdehyde (MDA) levels in G2, G3 and G4 were found to be decreased significantly when compared with G1 (P < 0.05). The SOD activities of G3 and G4 were higher when compared with G2 (P < 0.05). The number of sunburn cells (SBCs) was the highest in G2. Conclusions: Our results suggest that EGb 761 may have an important effect, both as a protective and therapeutic agent, in sunburn after UVB irradiation. [source]


Genomic scale analysis of the human keratinocyte response to broad-band ultraviolet-B irradiation

PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 1 2002
Joe Takao
Ultraviolet B (UVB) radiation is an important inducer of many biologic changes in skin, of which keratinocytes are a key target. To gain better insight into changes in gene expression generated in the early phase after UVB exposure, we used complementary RNA (cRNA) microarray hybridization to compare differences in mRNA expression of UVB-irradiated (single dose of 100 J/m2 broad-band UVB) and sham-irradiated primary cultured human keratinocytes. Six hours after irradiation, total RNA was isolated from keratinocytes, and cRNA was synthesized and hybridized to a GeneChip expression array (Affymetrix) consisting of 6800 genes. Based on a threshold of >,twofold change, 187 genes (2.8%) were designated to be the most UVB-responsive. Surprisingly, none of these genes had been shown previously to be modulated by UVB. Conversely, several genes in the microarray that had been reported previously to be UVB- responsive by other methods showed less (< twofold) or no change. Northern blotting of seven differentially modulated genes produced results similar to those derived from microarray technology, thereby validating the accuracy of screening. Clustering based on known or likely functions indicated that among 88 upregulated genes, nine encode for cytochrome c subunits, six for ribosomal proteins, and two for regulators of apoptosis. By contrast, many of the 99 downregulated genes are involved in transcription, differentiation and transport. These findings indicate that keratinocytes respond to a single low dose of broad-band UVB irradiation by enhancing processes involved in energy production and translation, while suppressing those related to transcription, differentiation and transport. [source]


Effects of Red Ginseng extract on ultraviolet B-irradiated skin change in C57BL mice

PHYTOTHERAPY RESEARCH, Issue 11 2008
Young Gon Kim
Abstract Red Ginseng (the roots of Panax ginseng C.A. Meyer) is used clinically in China, Korea and Japan for various diseases, including atherosclerosis, hypertension and stress etc. Although Red Ginseng roots have traditionally been thought to have antiageing effects, the basis for this hearsay is unclear. This study examined the effects of Red Ginseng extract on ultraviolet B (UVB)-irradiated skin ageing in mice. Oral administration of Red Ginseng extract (20 or 60 mg/kg, twice daily) prevented UVB-irradiated skin damage (increases of skin thickness and pigmentation, and reduction of skin elasticity). Furthermore, Red Ginseng extract inhibited the increases of epidermis and corium thickness induced by UVB irradiation. Red Ginseng extract inhibited the increase of skin TGF- ,1 content induced by UVB irradiation. These findings suggest that the protective action of Red Ginseng extract against UVB-irradiated skin ageing may be due partly to an inhibition of the increase of skin TGF- ,1 induced by UVB irradiation. In conclusion, the oral administration of Red Ginseng extract may be useful as a health supplement for protection against photoageing. Copyright © 2008 John Wiley & Sons, Ltd. [source]


Eumelanin and pheomelanin concentrations in human epidermis before and after UVB irradiation

PIGMENT CELL & MELANOMA RESEARCH, Issue 3 2005
Alison Hennessy
Summary Pheomelanin is widely thought to be causally related to susceptibility to the harmful effects of ultraviolet radiation: epidemiological studies show that those with a higher ratio of pheomelanin to eumelanin in hair have higher rates of melanoma, and work in mouse and cell culture shows that pheomelanin generates excess free radicals after UVR exposure. By contrast, based on measurements of eumelanin and pheomelanin in human skin, before and following irradiation, we now report that both pheomelanin and eumelanin are positively related to skin colour, and by inference, inversely with cancer susceptibility. The ratio of melanin classes is similar in people with widely different cancer rates and UVR sensitivity. Although our numbers are small, our results extend previous work in man, and lead us to speculate that factors other than the amount of pheomelanin may be important in determining UVR susceptibility in persons with red hair. [source]


A UVB-hypersensitive mutant in Arabidopsis thaliana is defective in the DNA damage response

THE PLANT JOURNAL, Issue 3 2009
Ayako N. Sakamoto
Summary To investigate UVB DNA damage response in higher plants, we used a genetic screen to isolate Arabidopsis thaliana mutants that are hypersensitive to UVB irradiation, and isolated a UVB-sensitive mutant, termed suv2 (for sensitive to UV 2) that also displayed hypersensitivity to ,-radiation and hydroxyurea. This phenotype is reminiscent of the Arabidopsis DNA damage-response mutant atr. The suv2 mutation was mapped to the bottom of chromosome 5, and contains an insertion in an unknown gene annotated as MRA19.1. RT-PCR analysis with specific primers to MRA19.1 detected a transcript consisting of 12 exons. The transcript is predicted to encode a 646 amino acid protein that contains a coiled-coil domain and two instances of predicted PIKK target sequences within the N-terminal region. Fusion proteins consisting of the predicted MRA19.1 and DNA-binding or activation domain of yeast transcription factor GAL4 interacted with each other in a yeast two-hybrid system, suggesting that the proteins form a homodimer. Expression of CYCB1;1:GUS gene, which encodes a labile cyclin:GUS fusion protein to monitor mitotic activity by GUS activity, was weaker in the suv2 plant after ,-irradiation than in the wild-type plants and was similar to that in the atr plants, suggesting that the suv2 mutant is defective in cell-cycle arrest in response to DNA damage. Overall, these results suggest that the gene disrupted in the suv2 mutant encodes an Arabidopsis homologue of the ATR-interacting protein ATRIP. [source]