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Vitamin D keratinocytes

Lazaros Belbasis, Irene Stefanaki, Alexander J Stratigos, Evangelos Evangelou
BACKGROUND: Skin cancers have a complex disease mechanism, involving both genetic and non-genetic risk factors. Numerous meta-analyses have been published claiming statistically significant associations between non-genetic risk factors and skin cancers without applying a thorough methodological assessment. OBJECTIVE: The present study maps the literature on the non-genetic risk factors of skin cancers, assesses the presence of statistical biases and identifies the associations with robust evidence...
September 13, 2016: Journal of Dermatological Science
Susana Cubillos, Johannes Norgauer
Psoriasis is an inflammatory skin disease with or without joint involvement. In this disease, the thickened epidermis and impaired barrier are associated with altered calcium gradients. Calcium and vitamin D are known to play important roles in keratinocyte differentiation and bone metabolism. Intracellular calcium is regulated by calcium-sensing receptor (CASR), calcium release-activated calcium modulator (ORAI) and stromal interaction molecule (STIM). Other proteins modulated by vitamin D play important roles in calcium regulation e...
October 2016: International Journal of Molecular Medicine
Justyna M Wierzbicka, Michał A Żmijewski, Anna Piotrowska, Boguslaw Nedoszytko, Magdalena Lange, Robert C Tuckey, Andrzej T Slominski
Ultraviolet radiation B stimulates both the production of vitamin D3 in the skin and the activation of the skin analog of the hypothalamic-pituitary-adrenal axis (HPA) as well as the central HPA. Since the role of vitamin D3 in the regulation of the HPA is largely unknown, we investigated the impact of 1,25(OH)2D3 and its noncalcemic analogs, 20(OH)D3 and 21(OH)pD, on the expression of the local HPA in human epidermal keratinocytes. The noncalcemic analogs showed similar efficacy to 1,25(OH)2D3 in stimulating the expression of neuropeptides, CRF, urocortins and POMC, and their receptors, CRFR1, CRFR2, MC1R, MC2R, MC3R and MC4R...
December 5, 2016: Molecular and Cellular Endocrinology
Daniel D Bikle, Yan Jiang, Thai Nguyen, Yuko Oda, Chia-Ling Tu
1,25 dihydroxyvitamin D (1,25(OH)2D), the active metabolite of vitamin D, and calcium regulate epidermal differentiation. 1,25(OH)2D exerts its effects through the vitamin D receptor (VDR), a transcription factor in the nuclear hormone receptor family, whereas calcium acts through the calcium sensing receptor (Casr), a membrane bound member of the G protein coupled receptor family. We have developed mouse models in which the Vdr and Casr have been deleted in the epidermis ((epid) Vdr (-∕-) and (epid) Casr (-∕-))...
2016: Frontiers in Physiology
Jörg Reichrath, Christos C Zouboulis, Thomas Vogt, Michael F Holick
Vitamin D represents one of the major driving factors for the development of life on earth and for human evolution. While up to 10-20 % of the human organism's requirements in vitamin D can be obtained by the diet (under most living conditions in the USA and Europe), approximately 90 % of all needed vitamin D has to be photosynthesized in the skin through the action of the sun (ultraviolet-B (UV-B)). The skin represents a key organ of the human body's vitamin D endocrine system (VDES), being both the site of vitamin D synthesis and a target tissue for biologically active vitamin D metabolites...
July 22, 2016: Reviews in Endocrine & Metabolic Disorders
Daniel Svensson, Daniel Nebel, Ulrikke Voss, Eva Ekblad, Bengt-Olof Nilsson
The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D3), has been reported to positively regulate the human cathelicidin anti-microbial peptide (CAMP) gene coding for LL-37, but the mechanisms are not completely understood. We have determined the expression of CAMP, vitamin D receptor (VDR), and the retinoid X receptor (RXR) isoforms in human skin and gingival tissue biopsies and investigated the signaling pathways involved in 1,25D3-induced upregulation of CAMP. Human skin and gingival biopsies exhibited few VDR-immunoreactive cells within the stratum basale, whereas rat colon enterocytes (positive control) possessed abundant VDR immunoreactivity...
June 30, 2016: Cell and Tissue Research
Jee-Bum Lee, Soo Hyeon Bae, Ki Rang Moon, Eui Young Na, Sook Jung Yun, Seung-Chul Lee
BACKGROUND: Cathelicidin (LL-37), Toll-like receptor 2 (TLR 2), and kallikreins (KLKs) are key inflammatory mediators in rosacea. Laser or light-based devices have been successfully used for rosacea. OBJECTIVE: We investigated the effects of light-emitting diodes (LED) on LL-37, KLKs, TLR 2, and protease activity in cultured normal human epidermal keratinocytes(NHEKs) and rosacea-like mouse skin(RLMS). METHODS: LL-37, KLK 5, KLK 7, and vitamin D receptor were induced by 1α,25-dihydroxyvitaminD3 (VD3 ) and TLR 2 by Ad-CMV transfection in cultured NHEKs...
June 17, 2016: Experimental Dermatology
Ester Ziv, Ruth Koren, Muayad A Zahalka, Amiram Ravid
Several inflammatory mediators increase calcitriol production by epidermal keratinocytes. In turn calcitriol attenuates the keratinocyte inflammatory response. Since the effect of the in-situ generated calcitriol depends also on the sensitivity to the hormone we studied the effect of inflammatory cytokines on the response of HaCaT human keratinocytes to calcitriol by examining the expression and transcriptional activity of VDR. Treatment with TNF, but not with IL-1β or interferon γ, increased VDR protein level, while decreasing the level of its heterodimerization partner RXRα...
January 2016: Dermato-endocrinology
Marwa M T Fawzi, Sara Bahaa Mahmoud, Shereen Fathi Ahmed, Olfat Gamil Shaker
BACKGROUND: Alopecia areata (AA) is a frequent autoimmune disease, the pathogenesis of which is still unknown. Androgenetic alopecia (AGA) is a noncicatricial type of patterned hair loss. Expression of vitamin D receptors (VDRs) on keratinocytes is essential for maintenance of normal hair cycle, especially anagen initiation. OBJECTIVE: To assess VDRs in the skin and blood of AA and AGA patients, in order to evaluate their possible role in these hair diseases. METHODS: This study recruited 20 patients with AA, 20 patients with AGA, and 20 healthy controls...
May 6, 2016: Journal of Cosmetic Dermatology
Lena A VON Schuckmann, Matthew H Law, Grant W Montgomery, Adele C Green, Jolieke C VAN DER Pols
BACKGROUND: The vitamin D endocrine system is implicated in skin carcinogenesis and polymorphisms in genes associated with the vitamin D receptor (VDR) gene may alter the risk of keratinocyte cancers (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)). MATERIALS AND METHODS: In a nested case-control study of 1,124 adults, we investigated associations between polymorphisms in VDR-related pathways and incident keratinocyte cancers during 11 years of follow-up using adjusted multivariate regression analysis...
May 2016: Anticancer Research
Anna Piotrowska, Justyna Wierzbicka, Tomasz Ślebioda, Michał Woźniak, Robert C Tuckey, Andrzej T Slominski, Michał A Żmijewski
Although the skin production of vitamin D is initiated by ultraviolet radiation type B (UVB), the role vitamin D plays in antioxidative or pro-oxidative responses remains to be elucidated. We have used immortalized human HaCaT keratinocytes as a model of proliferating epidermal cells to test the influence of vitamin D on cellular response to H2O2 or the anti-cancer drug, cisplatin. Incubation of keratinocytes with 1,25(OH)2D3 or its low calcemic analogues, 20(OH)D3, 21(OH)pD or calcipotriol, sensitized cells to ROS resulting in more potent inhibition of keratinocyte proliferation by H2O2 in the presence of vitamin D compounds...
June 2016: Steroids
Leila J Mady, Dare V Ajibade, Connie Hsaio, Arnaud Teichert, Chak Fong, Yongmei Wang, Sylvia Christakos, Daniel D Bikle
The role for 1,25-dihydroxyvitamin D3 and/or calcium in hair follicle cycling is not clear despite their impact on keratinocyte differentiation. We found that calbindin-D9k null (knockout) pups generated from calbindin-D9k knockout females fed a vitamin D-deficient, low-calcium (0.47%) diet develop transient alopecia. The pups appear phenotypically normal until 13 days of age, after which the hair progressively sheds in a caudocephalic direction, resulting in truncal alopecia totalis by 20-23 days, with spontaneous recovery by 28 days...
July 2016: Journal of Investigative Dermatology
Carlo Mattozzi, Giovanni Paolino, Antonio Giovanni Richetta, Stefano Calvieri
Psoriasis is a common, inflammatory, chronic, relapsing skin disease. Despite several hypotheses having been postulated to explain the pathogenesis of this disorder, nowadays it is considered as a T-cell-mediated disease; in this context an important role is played by vitamin D. The role of this micronutrient is important for many reasons: it is able to modulate the immune system; it is implicated in keratinocyte turnover; and it is involved in the integrity of the cutaneous barrier. In psoriasis, this molecule plays an important role due to its ability in the modulation of innate and adaptive immunity and by its antiproliferative and pro-differentiative effects on keratinocytes...
May 2016: Journal of Dermatology
Venil N Sumantran, Pratik Mishra, Rakesh Bera, Natarajan Sudhakar
Cytochrome P450 drug metabolizing enzymes are implicated in personalized medicine for two main reasons. First, inter-individual variability in CYP3A4 expression is a confounding factor during cancer treatment. Second, inhibition or induction of CYP3A4 can trigger adverse drug-drug interactions. However, inflammation can downregulate CYP3A4 and other drug metabolizing enzymes and lead to altered metabolism of drugs and essential vitamins and lipids. Little is known about effects of inflammation on expression of CYP450 genes controlling drug metabolism in the skin...
2016: Pharmaceutics
Anna Piotrowska, Justyna Wierzbicka, Michał A Żmijewski
Vitamin D plays important, pleiotropic role in the maintenance of global homeostasis. Its influence goes far beyond the regulation of calcium and phosphorus balance, as diverse activities of vitamin D and its natural metabolites assure proper functioning of major human organs, including skin. Recently, we reviewed the current understanding of vitamin D impact on human health from historical perspective (Wierzbicka et al. (2014) The renaissance of vitamin D. Acta Biochim Pol 61: 679-686). This article focuses on its functions in the skin...
2016: Acta Biochimica Polonica
Paolo Gisondi, Marco Di Mercurio, Luca Idolazzi, Giampiero Girolomoni
Psoriasis is a lifelong chronic inflammatory disease affecting 2-3% of the worldwide population. Current understanding of the pathogenesis of psoriasis assigns central importance to an interaction between acquired and innate immunity. The disease is characterized by a series of linked cellular changes in the skin, including hyperplasia of epidermal keratinocytes, angiogenesis, and infiltration of T lymphocytes, neutrophils, and other types of leukocytes in the affected skin. Plaque psoriasis is the most common clinical form and is characterized by red and scaly plaques generally localized at extensor sites such as elbows and knees...
November 2015: Journal of Rheumatology. Supplement
Leon H Kircik, Panagiotis Zografos
Psoriasis is a chronic inflammatory skin disease where the use of topical corticosteroids is a mainstream treatment. However, the continuous use of high potency topical corticosteroids is limited by a variety of well known adverse events which include, atrophy, and telangiectasia. Also, inhibition of lipid synthesis by steroids can cause impairment of the epidermal barrier, which is already disrupted in most of the inflammatory cutaneous disorders such as psoriasis. This will further lead to increase transepidermal water loss (TEWL), decreased hydration, dry skin, and irritation...
October 2015: Journal of Drugs in Dermatology: JDD
An-Sofie Vanherwegen, Gabriela Bomfim Ferreira, Elien Smeets, Yoko Yamamoto, Shigeaki Kato, Lut Overbergh, Conny Gysemans, Chantal Mathieu
The nuclear vitamin D receptor (VDR) is generally recognized as a ligand-dependent transcription factor that mediates the actions of its natural ligand, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) on multiple target genes involved in mineral homeostasis, bone development, as well as immune reactivity. As the VDR is widely distributed in nearly all cells of the body, it implies that the vitamin D endocrine system may regulate many cell types and functions. Experiments in VDR null mice established that the VDR has intrinsically critical roles in skin and keratinocyte biology but not in immune responses...
September 4, 2015: Journal of Steroid Biochemistry and Molecular Biology
H Zhang, H Lu, C Shrestha, Y Feng, Y Li, J Peng, Y Li, Z Xie
INTRODUCTION: Vitamin D and calcium are known to regulate differentiation and proliferation of keratinocytes; they might potentially have a role in suppressing carcinogenesis in squamous epithelium. Serum parathyroid hormone (pth) is a sensitive indicator of calcium and vitamin D deficiency, and 25-hydroxyvitamin D [25(OH)D] is an established marker of vitamin D status. METHODS: To determine whether levels of 25(OH)D, calcium, or pth in serum are associated with oral squamous cell carcinoma (oscc), we examined those parameters in serum collected from 70 patients with oscc and from an equal number of matched control subjects...
August 2015: Current Oncology
Amiram Ravid, Ohad Shenker, Efrat Buchner-Maman, Carmela Rotem, Ruth Koren
The active metabolite of vitamin D calcitriol and its analogs are well-known for their anti-inflammatory action in the skin, while their main side effect associated with topical treatment of inflammatory disorders is irritant contact dermatitis. Prostaglandin E2 (PGE2 ) is pro-inflammatory at the onset of inflammation and anti-inflammatory at its resolution. We hypothesized that induction of PGE2 synthesis by calcitriol in epidermal keratinocytes may contribute both to its pro-inflammatory and anti-inflammatory effects on the skin...
April 2016: Journal of Cellular Physiology
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