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The mechanisms whereby narrowband ultraviolet B (UVB) (311-313 nm, TL01) phototherapy are effective in psoriasis may differ from those occurring in broadband UVB phototherapy. In the present study, changes in epidermal cells as a result of TL01 therapy were assessed in the skin of patients with psoriasis. The non-lesional skin of five subjects with plaque psoriasis was biopsied before and after a series of 12 whole-body TL01 treatments. Following appropriate staining of skin sections, the numbers of p53-positive keratinocytes, sunburn cells and Langerhans cells in the epidermis were counted. TL01 therapy induced a threefold increase in the number of p53-positive epidermal cells, a 12-fold increase in sunburn cells and a twofold decrease in Langerhans cells. The increase in epidermal p53 expression and apoptosis of keratinocytes together with the depletion of Langerhans cells in the non-lesional skin of psoriasis patients are likely to contribute to the effectiveness of TL01 phototherapy.

Selenium (Se) has protective properties against ultraviolet (UV)-induced changes in skin cells in vitro but little is known about such activity in human subjects. In the present study, seven patients with psoriasis ingested 400 microg of sodium selenite daily during a 4 week course of whole-body narrow-band UVB (TL01) therapy while six more psoriasis patients, similarly irradiated, ingested a placebo. Skin biopsies, collected at the start and end of the phototherapy were analysed for phosphorylated p53, Fas, Bcl-2, Bax and oxidized guaninosine, and for numbers of Langerhans and sunburn cells. Following the TL01 therapy, no significant difference was observed for any of these markers when the Se group was compared with the placebo group of patients, although p53 and Bcl-2 expression decreased in the Se supplemented group.

Background: Ultraviolet (UV) radiation damages the cellular DNA of skin cells. In response, wild-type p53 protein accumulates in irradiated cells and the stabilized and transactivated protein can then induce genes involved in cell cycle arrest in G1, or in the initiation of apoptosis. Selenium protects cells from UVB-induced cell death and apoptosis by mechanisms which are unclear, although recent reports suggest that selenium protects against UV-induced cell damage by inducing DNA repair enzymes and transactivating p53., Methods: We examined whether selenomethionine could protect human skin cells from UV radiation-induced p53 transactivation, using a pRGCDeltafos-lacZ p53-dependent reporter construct stably transfected in an amelanotic melanoma cell line (Arn-8) which expresses wild-type p53. Cells were pretreated with or without selenomethionine and then irradiated with broadband UVB (approximately 270-350 nm); 0-30 mJ/cm2 from a Phillips TL100 W/12 lamp., Results: The percentage of cells with transcriptionally active p53 increased dose dependently up to 20 mJ/cm2 UVB. Treatment with 50 microM selenomethionine for 24 h both pre- and post-irradiation, significantly diminished p53 activation by 30-43% across the UV dose range (P=0.0085, n=5 independent experiments) and decreased UV-induced p53 protein accumulation as assessed by Western blotting., Conclusions: We conclude that selenomethionine inhibits broad band UVB-induced p53 transactivation and protein accumulation and that this effect correlates with reported protective effects of selenium against UV-induced DNA damage.

Leukemia inhibitory factor (LIF) is a polyfunctional cytokine with a variety and a diverse range of biological activities. However, this is a reflection of the fact that the cytokine is expressed in many different tissues, has a wide target cell range, and fulfills different functions in different tissues. The purpose of this article is to examine what is known about LIF expression in the skin and to consider whether LIF plays a role in inflammatory and hyperplastic events in the skin. LIF is strongly expressed in skin tumors, and recent studies indicate that it may affect tumor growth by several different mechanisms. The biological activities of LIF relevant to carcinogenesis, its expression, and signal transduction by the LIF receptor are described. Expression of LIF in normal skin by skin tumors and its induction by ultraviolet radiation and proinflammatory stimuli are discussed, as are possible interactions between LIF, mast cells, and tumor growth. We consider what role LIF and other members of the hemopoietin family of cytokines play in healthy and diseased skin and whether LIF could play a role in hyperplastic skin disorders. LIF appears to be an important cytokine for normal keratinocyte growth and wound healing and may be involved in regulating the proliferation of skin tumors. Accordingly, LIF may be a useful target for anticancer therapy and as a growth factor for normal skin during reconstructive surgery.

Immune suppression following UVB irradiation is partly attributed to the effects of the exposure on antigen-presenting cells. Following a single UVB irradiation, there is a decrease in epidermal Langerhans cell numbers; this is accompanied by an increase in the number of dendritic cells (DC) in lymph nodes draining the irradiated site. We investigated whether a similar effect occurred following multiple UVB exposures. Mice were irradiated on their ears and shaved dorsal skin twice a week for 3 weeks. After the final exposure, the number of ATPase(+) Langerhans cells in epidermal sheets prepared from the ears was found to be decreased by 33% compared to unirradiated controls. The number of DC in the draining lymph nodes (DLN) did not increase as might have been expected; rather, a significant decrease of approximately 30% in DC numbers in the DLN of UVB-irradiated mice compared with unirradiated controls occurred. This decrease in antigen-presenting cells in both the epidermis and the DLN may be an important contributing factor to the immune suppression that follows multiple UVB exposures.

Recent studies published in Oncogene and Proc. Natl. Acad. Sci. USA ascribe a role for selenium, acting through wild type p53, in protecting skin cells in culture from ultraviolet radiation-induced death. While selenium clearly protects cells against ultraviolet radiation-induced death, data that we present and discuss in this letter shows that wild type p53 is not required for such protection. Moreover the non-physiologically high levels of selenium used in some studies leads us to question the relevance of such effects for selenium-induced photoprotection.

A positive association between intake of calcium channel blockers and psoriasis has been observed recently. Intake of blockers of voltage-gated calcium ion channels is associated with outbreaks of psoriasis after a latent period in patients with and without a previous family history of psoriasis. This suggests that interfering with calcium influx may trigger psoriasis. Calcium influx also occurs via cyclic guanosine monophosphate-gated channels; human keratinocytes contain functional and non-functional (splice variants) versions of these channels. We show here that keratinocytes and skin from psoriatic individuals express higher levels of mRNA encoding a non-functional cyclic guanosine monophosphate-gated calcium channel and that high expression of the splice variant by transfection of cells in culture leads to loss of protein expression for the functional cyclic guanosine monophosphate-gated Ca2+ channels.