Activation of the aryl hydrocarbon receptor by TCDD inhibits senescence: A tumor promoting event?

Activation of the aryl hydrocarbon receptor (AHR) by the agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to promote tumor formation in both liver and skin. In the liver, but not the skin, the AHR-mediated events that contribute to TCDD’s tumor promoting activities have been studied in some detail and are thought to involve perturbation of cell fate processes. However, studies performed using cultured cells have often resulted in apparent contradictory results indicating that the impact of TCDD on cell fate processes may be cell context dependent. We and others have shown that in primary cultured keratinocytes TCDD increases post-confluent proliferation and increases late differentiation. Further, our studies performed in these cells indicate that TCDD can also inhibit culture-induced senescence. While senescence, a permanent cell cycle arrest, is emerging as an important process regulated by oncogenes and considered to be of therapeutic importance, its role with respect to TCDD/AHR mediated tumor promotion has not been fully considered. The intent of this article is to focus primarily on senescence as a cell process relevant to skin tumorigenesis and explore the idea that the inhibition of senescence by TCDD could be an important mechanism by which it may exert its tumor promoting effects in the skin.     

复方氟米松软膏联合UVB治疗寻常型银屑病的临床疗效观察

目的观察外涂氟米松软膏联合UVB照射治疗寻常型银屑病的疗效和安全性。方法治疗组于患处外涂氟米松软膏,每天2次,行UVB全身照射,隔日1次。对照组于患处外涂氟米松软膏,每天2次。结果治疗组有效率88.00%,对照组有效率60.00%,治疗组复发率19.05%,对照组复发率88.89%。结论复方氟米松软膏联合UVB照射治疗寻常型银屑病安全、有效,值得临床推广。     

Effects of ultraviolet light irradiation on the skin of MRL/l mice

Summary MRL/Mp-lpr/lpr (MRL/l) and MRL/Mp-+/+ mice were irradiated with middle-wavelength ultraviolet light (UVB), and the development of skin lesions, skin lupus band test (LBT), anti-DNA antibodies in sera, and the extent of glomerulonephritis of the kidney were examined. Long-term exposure to low doses of UVB irradiation accelerated the development of skin lesions and enhanced the intensity of the positive skin lupus band in MRL/l mice. The contents of anti-DNA antibodies in sera, the incidence of positive findings in LBT, and the extent of glomerulonephritis were not influenced by the UVB irradiation. The promotion of the development of the skin lesions in MRL/l mice by the UVB exposure was not considered to be associated with acceleration of systemic autoimmune phenomena.This is the twelfth part of a series of papers entitled Pathogenesis of Lupus Dermatoses in Autoimmune Mice     

Inhibitors of cysteine cathepsin and calpain do not prevent ultraviolet-B-induced apoptosis in human keratinocytes and HeLa cells

Caspases, members of the cysteine protease family, execute UVB-induced apoptosis in several cell lines and keratinocytes. Several researchers investigating UVB-induced apoptosis have demonstrated a dose-dependent protective effect of the synthetic peptide caspase inhibitor zVAD-fmk. However, zVAD-fmk displays a dose-dependent protective effect against UVB-induced apoptosis, even at doses higher than those required to block all known proapoptotic caspases. In addition, it is known that zVAD-fmk also inhibits other cysteine proteases including cathepsins and calpains, and these proteases have recently been demonstrated to play a role in the execution of programmed cell death induced by other stimuli, e.g. TNF-α. The purpose of the present study was therefore to investigate whether inhibitors of cysteine cathepsins and calpains could prevent UVB-induced apoptosis in HeLa cells and keratinocytes. This was done by investigating the effect of the irreversible cysteine protease inhibitor zFA-fmk, the cathepsin B inhibitor CA-074-Me and the calpain inhibitor ALLN on the viability of UVB-irradiated human keratinocytes and HeLa cells. At concentrations of 10 μM and above zVAD-fmk conferred partial dose-dependent protection against UVB-induced apoptosis in HeLa cells and keratinocytes. Moreover, caspase-3 activity was completely blocked at zVAD-fmk concentrations of 1 μM in HeLa cells. This indicates that caspase-independent mechanisms could be involved in UVB-induced apoptosis. However, the protease inhibitors zFA-fmk, CA-074-Me and ALLN all failed to prevent UVB-induced apoptosis in HeLa cells and keratinocytes. In conclusion, the protective effect of zVAD-fmk at high concentrations indicates that other proteases than caspases are active in the execution of UVB-induced apoptosis but further studies are needed to identify these proteases.     

P38 and JNK signal pathways are involved in the regulation of phlorizin against UVB‐induced skin damage

Phlorizin is well known to inhibit sodium/glucose cotransporters in the kidney and intestine for the treatment of diabetes, obesity and stress hyperglycaemia. However, the effects of phlorizin against ultraviolet B (UVB) irradiation and its molecular mechanism are still unknown. We examined the effects of phlorizin on skin keratinocyte apoptosis, reactive oxygen species (ROS) production, pro‐inflammatory responses after UVB irradiation and the changes of some signal molecules by in vitro and in vivo assay. We observed that phlorizin pretreatments inhibited HaCaT cell apoptosis and overproduction of ROS induced by UVB. Phlorizin also decreased the expression of UVB‐induced pro‐inflammatory cytokines, such as interleukin‐1 beta (IL‐1β), interleukin‐6 (IL‐6) and interleukin‐8 (IL‐8) at the mRNA level. Topical application of phlorizin on UVB‐exposed skin of nude mice prevented the formation of scaly skin and erythema, inhibited the increase of epidermal thickness and reduced acute inflammation infiltration in skin. Additionally, PCR, Western blot and immunohistochemical data showed that phlorizin reversed the overexpression of cyclooxygenase‐2 (Cox‐2) induced by UVB irradiation both in vitro and in vivo. The activation of p38 and JNK mitogen‐activated protein kinases (MAPK) after UVB irradiation was also inhibited by phlorizin. These findings suggest that phlorizin is effective in protecting skin against UVB‐induced skin damage by decreasing ROS overproduction, Cox‐2 expression and the subsequent excessive inflammation reactions. It seemed that p38 and JNK MAPK signal pathways are involved in the regulation of the protective function of phlorizin.     

Photo(chemo)therapy in private practice in Belgium, France and The Netherlands

Photo(chemo)therapy is used widely, and ultraviolet (UV) sources, protocols and indications are numerous. A survey was carried out to examine how photo(chemo)therapy is employed in private practice and to determine whether safety guidelines are respected. A questionnaire survey sent to Belgian, French and Dutch dermatologists generated 593 useful responses. UV sources, doses of UV and 8-methoxypsoralen (8-MOP), as well as the frequency of the treatment, were all different in the three countries. UV starting doses were rarely chosen according to the minimal phototoxic dose (MPD) or to the minimal erythema dose (MED). Total cumulative UV doses were not always determined. Maintenance PUVA therapy for psoriasis was still performed by 15 to 40% of dermatologists in the respective countries. Another striking fact was that genital protection is not universal. On the other hand, the irradiance of tubes is checked regularly, and contraindications are respected. Despite the availability of guidelines, clinicians seem to be inconstant in their assessment of the carcinogenic risk of UV radiation.     

Sunbed use in Buenos Aires, Argentina

The objectives were to survey tanning salons in a defined geographic area of Buenos Aires city and to assess the information offered to consumers regarding chronic exposure to ultraviolet radiation, types of radiation used, and safety measures employed. A prospective study using a standardized interview with limited multiple choice responses for data collection was conducted. Results of the interview survey were that 35% of the establishments (tanning salons) said they used UVA exclusively, 6% UVB, and 25% both; 35% did not know the type of radiation to which their clients were exposed. Sunbeds were promoted as healthy in 56% of the tanning salons, whereas potential risks were mentioned in only 15%. One to 3 sessions on the same day were allowed by 84%, while 40% allowed customers to choose the number of weekly sessions. The use of goggles was optional in 65% of the establishments and 21% did not even provide goggles. Use of sunscreens was not compulsory, and none of the salons had associated physicians. Previous history of skin cancer, sunburn or potential photosensitive drug intake were never recorded, and the age of access was not restricted in 71% of the establishments. In Argentina there are no guidelines to regulate the operation of tanning salon establishments or the equipment they use, and there are no specific measures taken to prevent skin and ocular pathologies. Ways to reduce the risks of ocular and skin pathologies from artificial tanning in Argentina are urgently needed.     

Protection against endogenous and UVB-induced oxidative damage in stratum corneum lipids by an antioxidant-containing cosmetic formulation

A 16-week human clinical study was carried out to determine the ability of antioxidants in a cosmetic vehicle to inhibit the induction of lipid peroxidation in stratum corneum lipids. The study consisted of a twice daily application of material for 12 weeks followed by a 4-week regression phase. Stratum corneum lipids were collected and then exposed to 500 mJ/cm2 of ultraviolet B (UVB) radiation in order to avoid excessive erythemal damage to the subjects. Lipid peroxides were assayed by a methylene blue derivative assay and expressed per unit area of skin. During the treatment period, decreases in the level of lipid peroxides were observed on the sites treated with the compositions containing antioxidants, as compared to the untreated sites, and expressed as percent differences. Decreases were observed in endogenous as well as UV-induced lipid peroxides followed by a return to baseline levels. These results demonstrate that antioxidants in a topical cosmetic formulation were effective in protecting human stratum corneum lipids against endogenous oxidation or if challenged by 500 mJ/cm2 UVB.