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Therapeutic wavelengths of ultraviolet B radiation activate apoptotic, circadian rhythm, redox signalling and key canonical pathways in psoriatic epidermis.

ABSTRACT: Ultraviolet B radiation (UVB) exerts pleiotropic effects on human skin. DNA damage response and repair pathways are activated by UVB; if damage cannot be repaired, apoptosis ensues. Although cumulative UVB exposure predisposes to skin cancer, UVB phototherapy is widely used as an effective treatment for psoriasis. Previous studies defined the therapeutic action spectrum of UVB and showed that psoriasis is resistant to apoptosis. This study aimed to investigate early molecular responses within psoriasis plaques following irradiation with single equi-erythemogenic doses of clinically-effective (311 nm, narrow-band) compared to clinically-ineffective (290 nm) UVB. Forty-eight micro-dissected epidermal samples from 20 psoriatic patients were analyzed using microarrays. Our bioinformatic analysis compared gene expression between 311 nm irradiated, 290 nm irradiated and control psoriasis epidermis to specifically identify 311 nm UVB differentially expressed genes (DEGs) and their upstream regulatory pathways. Key DEGs and pathways were validated by immunohistochemical analysis. There was a dynamic induction and repression of 311 nm UVB DEGs between 6 h and 18 h, only a limited number of DEGs maintained their designated expression status between time-points. Key disease and function pathways included apoptosis, cell death, cell migration and leucocyte chemotaxis. DNA damage response pathways, NRF2-mediated oxidative stress response and P53 signalling were key nodes, interconnecting apoptosis and cell cycle arrest. Interferon signalling, dendritic cell maturation, granulocyte adhesion and atherosclerotic pathways were also differentially regulated. Consistent with these findings, top transcriptional regulators of 311 nm UVB DEGs related to: a) apoptosis, DNA damage response and cell cycle control; b) innate/acquired immune regulation and inflammation; c) hypoxia/redox response and angiogenesis; d) circadian rhythmicity; f) EGR/AP1 signalling and keratinocyte differentiation; and g) mitochondrial biogenesis. This research provides important insights into the molecular targets of 311 nm UVB, underscoring key roles for apoptosis and cell death. These and the other key pathways delineated may be central to the therapeutic effects of 311 nm in psoriasis.

SUBMITTER: Addison R

PROVIDER: S-EPMC8050411 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Phototherapy is an effective therapy and may induce remission of psoriasis. Previous studies have established the action spectrum of clearance and that apoptosis is differentially induced in psoriasis plaques by clinically effective wavelengths of ultraviolet B (UVB). The aim of this study was to investigate the molecular mechanisms regulating psoriasis plaque resolution by studying the transcriptomic response to clinically effective (311nm, narrow band) UVB compared to a clinically ineffective (290nm) wavelength. We irradiated lesional psoriatic skin in vivo with a single 3 MED (minimal erythemal dose) of 311nm or 290nm wavelength of UVB and performed skin biopsies at 4h or 18h post irradiation and from un-irradiated lesional skin. Forty-eight micro-dissected epidermal samples were analysed using the Illumina DASL array platform from 20 psoriatic patients. Bioinformatic analysis identified differentially expressed genes (DEGs) associated with 311nm but not 290nm irradiation; these DEGs were subject to Ingenuity pathway and upstream regulator analysis. The number of differentially regulated epidermal genes was greatest at 18h following UVB, after irradiation with clinically effective (311nm) UVB. The main pathways differentially affected by 311nm UVB only were apoptosis, necrosis, acute phase signalling, p53 signalling and chemotaxis. The greatest fold change observed was a 7.5 fold increase in expression of CDKN1A (WAF1/ p21), the p53 target gene, following irradiation with 311nm UVB but not 290nm (clinically ineffective UVB). Acute phase, LXR and PTEN signalling, dendritic cell maturation, granulocyte adhesion and atherosclerotic pathways were also differentially regulated by 311nm compared to 290nm UVB. This work provides insight into the molecular mechanisms regulating psoriatic remodelling in response to UV phototherapy, supports a key role for apoptosis and cell death in psoriasis plaque clearance, and identifies a number of novel therapeutic pathways. Further studies may lead to development of potential biomarkers to assess which patients are more likely to respond to UVB.

Project description:Psoriasis is a chronic inflammatory skin disease characterized by exaggerated keratinocyte proliferation. Current opinion indicates that psoriasis is driven by T cell-mediated immune responses targeting keratinocytes. However, psoriasis cannot be explained solely on the basis of T-cell activation, and it is likely that an intrinsic alteration in epidermal keratinocytes plays a very important role in disease expression. Syndecans comprise a major family of cell surface heparan sulfate proteoglycans. Several studies indicate their role in adhesion, cell-extracellular matrix interactions, migration, keratinocyte proliferation and differentiation, inflammation, and wound healing. To determine the expression of syndecan-1 in psoriasis, skin samples from 29 patients with fully developed psoriasis and skin samples from 14 healthy volunteer persons with no personal or family history of psoriasis were immunohistochemically examined using monoclonal antibody against syndecan-1. The expression of syndecan-1 was analyzed in whole mount section of psoriatic and non-psoriatic skin biopsies under high magnification (400x). In addition, the intensity and topography of reaction in the cell, as well as localization of positive cells in the epidermis were evaluated. Strong syndecan-1 reactivity in epidermal cells in all non-psoriatic and psoriatic samples was observed. Statistical analysis showed no significant differences between two analyzed groups (P > 0.05). In normal skin syndecan-1 was expressed in full thickness of the epidermis. The strongest reaction was observed in membranes and intercellular junctions of spinous and granular layer while basal cells showed weaker expression that was confined to cytoplasm. In psoriatic skin syndecan-1 was expressed in the membrane and intercellular junction of cells located in thickened and elongated rete ridges of the epidermis. The strongest reaction was in basal and suprabasal layers and expression diminished through spinous layer. Cells in spinous layer lose syndecan-1 expression, which is opposite pattern to normal skin. Our results suggest that aberrant skin expression of syndecan-1 may be involved in the development of psoriasis.

Project description:Qualities of the light environment, such as the spectral composition of light, have been shown to impact growth and performance of broiler chickens. UVA light is visible to broiler chickens, whereas UVB wavelengths promote endogenous vitamin D synthesis, which could support their rapid development. The aim of the current study was to investigate the impacts of supplementary UVA and UVB wavelengths on performance indicators of broiler chickens. Day-old Ross 308 chicks (n = 638), reared to a target stocking density of 33 kg/m2, were randomly assigned to 1 of 3 lighting treatments: A) White light emitting diode (LED) and supplementary UVA LED lighting (18-h photoperiod); B) White LED with supplementary UVA and UVB fluorescent lighting providing 30 μW/cm2 UVB at bird level (lights on for 8 h of the total photoperiod to avoid overexposure of UVB); and C) White LED control group, representative of farm conditions (18-h photoperiod). Mortality was recorded, and broiler chickens were individually weighed at 8, 15, 22, 27, and 34 D of age. Generalized linear models and nonlinear mixed effects models (Gompertz curve) were fitted to determine the effects of UV wavelengths on broiler mortality and growth performance. UV did not impact breast or leg weight of broiler chickens but was associated with differences in mortality, growth, and end weight. Broiler chickens provided with UVA for the full 18-h photoperiod had slower initial growth than control broilers and a reduction in mortality. Results from male broilers reared with supplementary UVA + UVB for 8 h indicated they could reach finishing weights sooner than controls, which supports the potential for UVA + B to improve the growth performance of males. Results suggest that the provision of supplementary UVA + UVB wavelengths may improve the performance of male broiler chickens. The reduction in mortality in the UVA only treatment may warrant further investigation. The inclusion of UV wavelengths within poultry lighting regimes represents a promising area of further study.

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Therapeutic wavelengths of ultraviolet B radiation activate apoptotic, circadian rhythm, redox signalling and key canonical pathways in psoriatic epidermis.

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