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Oral vitamin D for the attenuation of sunburn

ABSTRACT: Background: The diverse immunomodulatory effects of vitamin D are increasingly being recognized. However, the ability of oral vitamin D to modulate immune responses in vivo has not been established in humans. Methods: Twenty healthy adults were randomized to receive placebo or a single high dose of vitamin D3 (cholecalciferol) one hour after localized skin irradiation with an erythemogenic dose of ultraviolet radiation. Primary outcomes included skin redness, skin thickness, and tissue expression of inflammatory mediators (TNF-α and iNOS). Secondary outcomes included microarray analyses. Results: As compared to placebo, subjects receiving vitamin D3 (200,000 IU) demonstrated reduced expression of TNF-α (p=0.04) and iNOS (p=0.02) in skin biopsies 48 hours after ultraviolet light exposure. Demonstrated trends included reduced skin redness (p=0.17), and reduced skin thickness (p=0.09) in subjects receiving vitamin D3 (200,000 IU). Unsupervised clustering of individuals based on global gene expression revealed that subjects with enhanced skin barrier repair expression profiles had higher serum vitamin D3 levels (p=0.007), increased arginase expression (p=0.005), and a sustained reduction in skin redness (p=0.02) after treatment, as compared to subjects with enhanced inflammatory gene expression profiles. Conclusions: A single high dose of oral vitamin D is capable of attenuating a local sunburn response to ultraviolet radiation, suggesting that oral vitamin D may be clinically therapeutic for its immunomodulatory properties. These results have broad implications for the role of vitamin D in skin homeostasis, and implicate arginase activation as a novel mechanism by which vitamin D exerts anti-inflammatory effects in humans.

ORGANISM(S): Homo sapiens

PROVIDER: GSE86406 | GEO | 2018/02/16

REPOSITORIES: GEO

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Project description:Background: In addition to its canonical functions, vitamin D has been proposed to be an important mediator of the immune system. Despite ample sunshine, vitamin D deficiency is prevalent (> 80%) in the Middle East, resulting in a high rate of supplementation. However, the underlying molecular mechanisms of the specific regimen and potential factors affecting an individual’s response to vitamin D are not well characterized. Objective: To characterize changes in blood transcriptomic and the potential mechanisms associated with vitamin D3 supplementation and response. Design: In this intervention study, one hundred vitamin D-deficient women were given a weekly oral dose (50,000 IU) of vitamin D3 for three months. A high-throughput targeted PCR, composed of 264 genes representing important blood transcriptomic fingerprints in health and disease states, was performed on pre- and post-supplementation blood samples to profile the molecular response to vitamin D3. Multivariate, network, gene ontology, and literature mining analyses were used for the interpretation of the transcriptomic profiling results. Results: We identified 54 differentially expressed genes that were strongly modulated by vitamin D3 supplementation. Network analyses showed significant changes in the immune-related pathways such as TLR4/CD14 and IFN receptors, and catabolic processes related to NFkB, which were subsequently confirmed by gene ontology enrichment analyses. We proposed a model for vitamin D3 response, using the reduced expression of the molecules involved and the receptor-mediated intra-cellular signaling leading to reduce cytokine production. Conclusions: Blood-transcriptomic profiles of vitamin D3 response were generated using a targeted blood gene panel. Vitamin D has a strong effect on the immune system, G-coupled protein receptor signaling, and the ubiquitin system. We highlighted the major molecular changes and biological processes induced by vitamin D3, which will help to further investigate the effectiveness of vitamin D supplementation among individuals in the Middle East.

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Oral vitamin D for the attenuation of sunburn

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