%0 Journal Article %~ PubMed %A Sequeira, Vanessa B %A Rybchyn, Mark S %A Gordon-Thomson, Clare %A Tongkao-On, Wannit %A Mizwicki, Mathew T %A Norman, Anthony W %A Reeve, Vivienne E %A Halliday, Gary M %A Mason, Rebecca S %T Opening of Chloride Channels by 1α,25-Dihydroxyvitamin D(3) Contributes to Photoprotection against UVR-Induced Thymine Dimers in Keratinocytes. %B Journal of Investigative Dermatology %D 2013 %C United States %I Nature Publishing Group %V 133 %N 3 %P 776-782 %@ 1523-1747 %X %Z FOR Codes: 606 %0 Journal Article %~ PubMed %A Mason, Rebecca S %A Reichrath, Jörg %T Sunlight Vitamin D and Skin Cancer. %B Anticancer Agents in Medicinal Chemistry %D 2013 %C The Netherlands %I Bentham Science Publishers Ltd. %V 13 %N 1 %P 83-97 %@ 1875-5992 %X %Z FOR Codes: 110306 110304 %0 Journal Article %~ PubMed %A Gordon-Thomson, Clare %A Gupta, Ritu %A Tongkao-On, Wannit %A Ryan, Anthony %A Halliday, Gary M %A Mason, Rebecca S %T 1α,25 Dihydroxyvitamin D(3) enhances cellular defences against UV-induced oxidative and other forms of DNA damage in skin. %B Photochemical & Photobiological Sciences %D 2012 %C United Kingdom %I RSC Publications %V 11 %N 12 %P 1837-1847 %@ 1474-9092 %X %Z FOR Codes: 60699 110306 %0 Journal Article %A Zavgorodniy, Alexander %A Mason, Rebecca %A LeGeros, Racquel Z %A Rohanizadeh, Ramin %T Adhesion of a chemically deposited monetite coating to a Ti substrate %B Surface and Coatings Technology %D 2012 %C Switzerland %I Elsevier S.A. %V 206 %N 21 %P 4433-4438 %@ 0257-8972 %X %Z FOR Codes: 111501 %0 Journal Article %~ PubMed %A Wilson, Nicholas M %A Hilmer, Sarah N %A March, Lyn M %A Chen, Jian Sheng %A Gnjidic, Danijela %A Mason, Rebecca S %A Cameron, Ian D %A Sambrook, Philip N %T Associations between drug burden index and mortality in older people in residential aged care facilities. %B Drugs & Aging %D 2012 %C New Zealand %I Adis International Ltd. %V 29 %N 2 %P 157-165 %@ 1170-229X %X The Drug Burden Index (DBI), a measure of an individual''s exposure to anticholinergic and sedative medications, is associated with functional impairment in community-dwelling, older people. In people from residential aged care facilities (RACFs), DBI score does not appear to be associated with functional impairment, but is associated with an increased risk of falls. %Z FOR Codes: 110308 %0 Journal Article %~ PubMed %A Dixon, Katie M %A Sequeira, Vanessa B %A Deo, Shivashni S %A Mohan, Ritu %A Posner, Gary H %A Mason, Rebecca S %T Differential photoprotective effects of 1,25-dihydroxyvitamin D3 and a low calcaemic deltanoid. %B Photochemical & Photobiological Sciences %D 2012 %C United Kingdom %I Royal Society of Chemistry %V 11 %N 12 %P 1825-1830 %@ 1474-9092 %X We have previously demonstrated that the active vitamin D hormone, 1??,25-dihydroxyvitamin D3 (1,25(OH)(2)D(3)) and a cis-locked non-genomic analogue, protect skin cells from ultraviolet radiation (UV)-induced skin cell loss, DNA damage, immunosuppression and skin carcinogenesis. Herein, we used a low-calcaemic analogue, 1??-hydroxymethyl-16-ene-24,24-difluoro-25-hydroxy-26,27-bis-homovitamin D3 (QW), which has some transactivating capacity and is approximately 80-100 times less calcaemic than 1,25(OH)(2)D(3). QW (0.1-10 nM) significantly (p < 0.05-0.01) reduced UV-induced DNA lesions (CPD) in skin fibroblasts and keratinocytes and reduced cell death after UV exposure. Moreover, both 1,25(OH)(2)D(3) and QW (1 nM) were equally effective in significantly (p < 0.01) increasing levels of tumour suppressive p53 in cultured human keratinocytes at 3 and 6 h after UV exposure. In a hairless mouse model, both 1,25(OH)(2)D(3) and QW (22.8 ??mol cm(-2)) reduced UV-immunosuppression from 13.7 ?? 1.3% to 0.1 ?? 1.1% (p < 0.01) and 5.4 ?? 1.5% (p < 0.01) respectively. When tested alongside 1,25(OH)(2)D(3) in a murine model of skin carcinogenesis. QW (22.8 ??mol cm(-2)) was not as effective as 1??,25(OH)(2)D(3) or a cis-locked analogue in reducing tumour formation or inhibiting tumour progression. It is possible that the dose required for QW to be effective as an anti-photocarcinogenesis agent in vivo is higher than for protection against the acute effects of UV exposure, but the dissociation between clear acute photo-protective effects and limited long term photoprotection is as yet unexplained. %Z FOR Codes: 110306 111603 %0 Journal Article %~ PubMed %A Sambrook, P N %A Cameron, I D %A Chen, J S %A Cumming, R G %A Durvasula, S %A Herrmann, M %A Kok, C %A Lord, S R %A Macara, M %A March, L M %A Mason, R S %A Seibel, M J %A Wilson, N %A Simpson, J M %T Does increased sunlight exposure work as a strategy to improve vitamin D status in the elderly: a cluster randomised controlled trial. %B Osteoporosis International %D 2012 %C United Kingdom %I Springer UK %V 23 %N 2 %P 615-624 %@ 1433-2965 %X Sunlight exposure by improving vitamin D status could be a simple public health strategy in reducing falls among frail elder people. In a randomised controlled trial, adherence to sunlight exposure was low (median adherence, 26%) and no effect of increased UV exposure on falls risk was observed (incidence rate ratio (IRR) 1.06, P???=???0.73). INTRODUCTION: This study aimed to determine whether increased sunlight exposure was effective to improve vitamin D status and reduce falls in the elderly. METHODS: In a cluster randomised controlled trial (NCT00322166 at ClinicalTrials.gov), 602 residents aged 70 or more (mean age, 86.4??years; 71% female) were recruited from 51 aged care facilities in Northern Sydney, Australia. Participants were randomised by facility to receive either increased sunlight exposure (additional 30-40??min/day in the early morning) with (UV+) or without (UV) calcium supplementation (600??mg/day) or neither (control) for a year. The co-primary endpoints were change in serum 25 hydroxy vitamin D (25OHD) and falls incidence after 12??months. RESULTS: Adherence to sunlight exposure was low (median adherence, 26%; IQR, 7%-45%). Serum 25OHD levels were low at baseline (median, 32.9??nmol/L) and increased only slightly depending on the number of sunlight sessions attended over 12??months (P???=???0.04). During the study, 327 falls occurred in 111 (54%) subjects in the control group, 326 falls in 111 (58%) subjects in the UV only group and 335 falls in 108 (52%) subjects in the UV+ group. By intention-to-treat analysis, there was no significant effect of increased UV exposure on falls risk (IRR, 1.06; 95% CI, 0.76-1.48; P???=???0.73). However, in 66 participants who attended ???130 sessions per year (adherence, ???50% of 260 sessions-five per week), falls were significantly reduced (IRR, 0.52; 95% CI, 0.31-0.88; P???=???0.01) compared with the control group. CONCLUSIONS: Increased sunlight exposure did not reduce vitamin D deficiency or falls risk in frail older people. This public health strategy was not effective most likely due to poor adherence to the intervention. %Z FOR Codes: 110308 111716 %0 Journal Article %~ PubMed %A Sequeira, Vanessa B %A Rybchyn, Mark S %A Tongkao-On, Wannit %A Gordon-Thomson, Clare %A Malloy, Peter J %A Nemere, Ilka %A Norman, Anthony W %A Reeve, Vivienne E %A Halliday, Gary M %A Feldman, David %A Mason, Rebecca S %T The role of the vitamin D receptor and ERp57 in photoprotection by 1??,25-dihydroxyvitamin D3. %B Molecular Endocrinology %D 2012 %C United States %I The Endocrine Society %V 26 %N 4 %P 574-582 %@ 1944-9917 %X UV radiation (UVR) is essential for formation of vitamin D(3), which can be hydroxylated locally in the skin to 1??,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)]. Recent studies implicate 1,25-(OH)(2)D(3) in reduction of UVR-induced DNA damage, particularly thymine dimers. There is evidence that photoprotection occurs through the steroid nongenomic pathway for 1,25-(OH)(2)D(3) action. In the current study, we tested the involvement of the classical vitamin D receptor (VDR) and the endoplasmic reticulum stress protein 57 (ERp57), in the mechanisms of photoprotection. The protective effects of 1,25-(OH)(2)D(3) against thymine dimers were abolished in fibroblasts from patients with hereditary vitamin D-resistant rickets that expressed no VDR protein, indicating that the VDR is essential for photoprotection. Photoprotection remained in hereditary vitamin D-resistant rickets fibroblasts expressing a VDR with a defective DNA-binding domain or a mutation in helix H1 of the classical ligand-binding domain, both defects resulting in a failure to mediate genomic responses, implicating nongenomic responses for photoprotection. Ab099, a neutralizing antibody to ERp57, and ERp57 small interfering RNA completely blocked protection against thymine dimers in normal fibroblasts. Co-IP studies showed that the VDR and ERp57 interact in nonnuclear extracts of fibroblasts. 1,25-(OH)(2)D(3) up-regulated expression of the tumor suppressor p53 in normal fibroblasts. This up-regulation of p53, however, was observed in all mutant fibroblasts, including those with no VDR, and with Ab099; therefore, VDR and ERp57 are not essential for p53 regulation. The data implicate the VDR and ERp57 as critical components for actions of 1,25-(OH)(2)D(3) against DNA damage, but the VDR does not require normal DNA binding or classical ligand binding to mediate photoprotection. %Z FOR Codes: 110306 %0 Journal Article %A Brock, Kaye %A Mason, Rebecca %A Ke, Liang %A Koo, Fung %A Jang, Haeyoung %A Clemson, Lindy %A Mpofu, Elias %A Tseng, Marilyn %A Fraser, David %A Seibel, Markus %T Vitamin D and Metabolic Syndrome in Immigrant East Asian Women Living in Sydney, Australia: A Pilot %B Journal of Metabolic Syndrome %D 2012 %C United States %I Omics Publishing Group %V 1 %N 1 %P 103 %@ 2167-0943 %X %Z FOR Codes: 1117 110107 %0 Book Section %A Dixon, Katie %A Sequeira, Vanessa B %A Camp, Aaron %A Mason, Rebecca %T Vitamin D and Skin Cancer %B Handbook of Diet, Nutrition and the Skin %D 2012 %C Netherlands %I Springer %V %N %P 394-411 %@ 9789086867295 %E Preedy, Victor R. %E Preedy, Victor R. %E Preedy, Victor R. %E Preedy, Victor R. %E Preedy, Victor R. %E Preedy, Victor R. %X %Z FOR Codes: 110304 111201 %0 Journal Article %~ PubMed %A Nowson, Caryl A %A McGrath, John J %A Ebeling, Peter R %A Haikerwal, Anjali %A Daly, Robin M %A Sanders, Kerrie M %A Seibel, Markus J %A Mason, Rebecca S %A , Working Group of Australian and New Zealand Bone and Mineral Society, Endocrine Society of Australia and Osteoporosis Australia %T Vitamin D and health in adults in Australia and New Zealand: a position statement. %B The Medical Journal of Australia %D 2012 %C Australia %I Australasian Medical Publishing Company Pty. Ltd. %V 196 %N 11 %P 686-687 %@ 1326-5377 %X The prevalence of vitamin D deficiency varies, with the groups at greatest risk including housebound, community-dwelling older and/or disabled people, those in residential care, dark-skinned people (particularly those modestly dressed), and other people who regularly avoid sun exposure or work indoors. Most adults are unlikely to obtain more than 5%-10% of their vitamin D requirement from dietary sources. The main source of vitamin D for people residing in Australia and New Zealand is exposure to sunlight. A serum 25-hydroxyvitamin D (25-OHD) level of ? 50 nmol/L at the end of winter (10-20 nmol/L higher at the end of summer, to allow for seasonal decrease) is required for optimal musculoskeletal health. Although it is likely that higher serum 25-OHD levels play a role in the prevention of some disease states, there is insufficient evidence from randomised controlled trials to recommend higher targets. For moderately fair-skinned people, a walk with arms exposed for 6-7 minutes mid morning or mid afternoon in summer, and with as much bare skin exposed as feasible for 7-40 minutes (depending on latitude) at noon in winter, on most days, is likely to be helpful in maintaining adequate vitamin D levels in the body. When sun exposure is minimal, vitamin D intake from dietary sources and supplementation of at least 600 IU (15 µg) per day for people aged ? 70 years and 800 IU (20 µg) per day for those aged > 70 years is recommended. People in high-risk groups may require higher doses. There is good evidence that vitamin D plus calcium supplementation effectively reduces fractures and falls in older men and women. %Z FOR Codes: 111712 %0 Journal Article %~ PubMed %A Winzenberg, Tania %A van der Mei, Ingrid %A Mason, Rebecca S %A Nowson, Caryl %A Jones, Graeme %T Vitamin D and the musculoskeletal health of older adults. %B Australian Family Physician %D 2012 %C Australia %I Royal Australian College of General Practitioners %V 41 %N 3 %P 92-99 %@ 0300-8495 %X The scientific literature related to vitamin D and bone health in older adults is extensive. %Z FOR Codes: 110306 %0 Journal Article %~ PubMed %A Mason, Rebecca S %T Vitamin D: one size does not fit all. %B Clinical Endocrinology %D 2012 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 76 %N 3 %P 326-327 %@ 0300-0664 %X %Z FOR Codes: 606 1103 1116 %0 Journal Article %~ PubMed %A Dixon, Katie M %A Norman, Anthony W %A Sequeira, Vanessa B %A Mohan, Ritu %A Rybchyn, Mark S %A Reeve, Vivienne E %A Halliday, Gary M %A Mason, Rebecca S %T 1{alpha},25(OH)2-vitamin D and a non-genomic vitamin D analog inhibit ultraviolet radiation-induced skin carcinogenesis. %B Cancer prevention research (Philadelphia, Pa.) %D 2011 %C United States %I American Association for Cancer Research %V 4 %N 9 %P 1485-94 %@ 1940-6215 %X Exposure to ultraviolet radiation (UVR) can lead to a range of deleterious responses in the skin. An important form of damage is the DNA photolesion cyclobutane pyrimidine dimer (CPD). CPDs can be highly mutagenic if not repaired prior to cell division and can lead to UV-induced immunosuppression, making them potentially carcinogenic. UVR exposure also produces vitamin D, a prehormone. Different shapes of the steroid hormone 1??,25-dihydroxyvitamin D??? [1,25(OH)???D???] can produce biological responses through binding either to its cognate nuclear receptor (VDR) to regulate gene transcription or to the VDR associated with plasma membrane caveolae to produce, via signal transduction, nongenomic physiologic responses. Here, we show that both 1,25(OH)???D??? and 1??,25(OH)???-lumisterol (JN), a conformationally restricted analogue that can generate only nongenomic responses, are effective inhibitors of UV damage in an immunocompetent mouse (Skh:hr1) model susceptible to UV-induced tumors. Both 1,25(OH)???D??? and JN significantly reduced UVR-induced CPD, apoptotic sunburn cells, and immunosuppression. Furthermore, these compounds inhibited skin tumor development, both papillomas and squamous cell carcinomas, in these mice. The observed reduction of these UV-induced effects by 1,25(OH)???D??? and JN suggests a role for these compounds in prevention against skin carcinogenesis. To the best of our knowledge, this is the first comprehensive report of an in vivo long-term biological response generated by chronic dosing with a nongenomic-selective vitamin D steroid. %Z FOR Codes: 111603 %0 Journal Article %~ PubMed %A Rybchyn, Mark S %A Slater, Michael %A Conigrave, Arthur D %A Mason, Rebecca S %T An Akt-dependent increase in canonical Wnt signalling and a decrease in sclerostin protein levels are involved in strontium ranelate-induced osteogenic effects in human osteoblasts. %B The Journal of biological chemistry %D 2011 %C United States %I American Society for Biochemistry and Molecular Bi %V 286 %N 27 %P 23771-9 %@ 1083-351X %X Sclerostin is an important regulator of bone homeostasis and canonical Wnt signaling is a key regulator of osteogenesis. Strontium ranelate is a treatment for osteoporosis that has been shown to reduce fracture risk, in part, by increasing bone formation. Here we show that exposure of human osteoblasts in primary culture to strontium increased mineralization and decreased the expression of sclerostin, an osteocyte-specific secreted protein that acts as a negative regulator of bone formation by inhibiting canonical Wnt signaling. Strontium also activated, in an apparently separate process, an Akt-dependent signaling cascade via the calcium-sensing receptor that promoted the nuclear translocation of ??-catenin. We propose that two discrete pathways linked to canonical Wnt signaling contribute to strontium-induced osteogenic effects in osteoblasts. %Z FOR Codes: 60602 304 %0 Journal Article %~ PubMed %A Wilson, Nicholas M %A Hilmer, Sarah N %A March, Lyn M %A Cameron, Ian D %A Lord, Stephen R %A Seibel, Markus J %A Mason, Rebecca S %A Chen, Jian Shen %A Cumming, Robert G %A Sambrook, Philip N %T Associations Between Drug Burden Index and Falls in Older People in Residential Aged Care. %B Journal of the American Geriatrics Society %D 2011 %C United States %I Wiley-Blackwell Publishing, Inc. %V 59 %N 5 %P 875-880 %@ 0002-8614 %X To evaluate the association between the Drug Burden Index (DBI), a measure of a person''s total exposure to anticholinergic and sedative medications that includes principles of dose-response and maximal effect and is associated with impaired physical function in community-dwelling older people, and falls in residents of residential aged care facilities (RACFs). %Z FOR Codes: 1103 1115 %0 Journal Article %~ PubMed %A Brock, Kaye E %A Huang, Wen-Yi %A Fraser, David R %A Ke, Liang %A Tseng, Marilyn %A Mason, Rebecca S %A Stolzenberg-Solomon, Rachael Z %A Michal Freedman, D %A Ahn, Jiyoung %A Peters, Ulrike %A McCarty, Catherine %A Hollis, Bruce W %A Ziegler, Regina G %A Purdue, Mark P %A Graubard, Barry I %T Diabetes prevalence is associated with serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in US middle-aged Caucasian men and women: a cross-sectional analysis within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. %B The British journal of nutrition %D 2011 %C United Kingdom %I Cambridge University Press %V 106 %N 3 %P 339-44 %@ 0007-1145 %X Hypovitaminosis D may be associated with diabetes, hypertension and CHD. However, because studies examining the associations of all three chronic conditions with circulating 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) are limited, we examined these associations in the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (n 2465). Caucasian PLCO participants selected as controls in previous nested case-control studies of 25(OH)D and 1,25(OH)(2)D were included in this analysis. Diabetes, CHD and hypertension prevalence, risk factors for these conditions and intake of vitamin D and Ca were collected from a baseline questionnaire. Results indicated that serum levels of 25(OH)D were low (< 50 nmol/l) in 29 % and very low (< 37 nmol/l) in 11 % of subjects. The prevalence of diabetes, hypertension and CHD was 7, 30 and 10 %, respectively. After adjustment for confounding by sex, geographical location, educational level, smoking history, BMI, physical activity, total dietary energy and vitamin D and Ca intake, only diabetes was significantly associated with lower 25(OH)D and 1,25(OH)(2)D levels. Caucasians who had 25(OH)D ??? 80 nmol/l were half as likely to have diabetes (OR 0??5 (95 % CI 0??3, 0??9)) compared with those who had 25(OH)D < 37 nmol/l. Those in the highest quartile of 1,25(OH)(2)D (??? 103 pmol/l) were less than half as likely to have diabetes (OR 0??3 (95 % CI 0??1, 0??7)) than those in the lowest quartile (< 72 pmol/l). In conclusion, the independent associations of 25(OH)D and 1,25(OH)(2)D with diabetes prevalence in a large population are new findings, and thus warrant confirmation in larger, prospective studies. %Z FOR Codes: 110306 %0 Journal Article %A Mak, Jenson CS %A Mason, Rebecca %A Klein, Linda %A Cameron, Ian %T Improving mobility and reducing disability in older people through early high-dose vitamin D replacement following hip fracture: A protocol for a randomized controlled trial and economic evaluation %B Geriatric Orthopaedic Surgery & Rehabilitation %D 2011 %C United Kingdom %I Sage Publications Ltd. %V 2 %N 3 %P 94-99 %@ 2151-4585 %X %Z FOR Codes: 110308 110321 %0 Journal Article %A Wilson, Nicholas %A Hilmer, Sarah %A March, Lyn %A Cameron, Ian %A Lord, Stephen %A Mason, Rebecca %A Sambrook, Philip %T Physical functioning measures and risk of falling in older people living in residential aged care facilities %B Therapeutic Advances in Musculoskeletal Disease %D 2011 %C United Kingdom %I Sage Publications Ltd. %V 3 %N 1 %P 9-15 %@ 1759-7218 %X %Z FOR Codes: 111718 110321 %0 Book Section %A Mason, Rebecca %A Dixon, Katie %A Sequeira, Vanessa B %A Gordon-Thomson, Clare %T Sunlight Protection by Vitamin D Compounds %B Vitamin D, 3rd Ed %D 2011 %C United States %I Elsevier Inc. %V %N %P 1943-1945 %@ 9780123870346 %E Feldman, David %E Pike, J.Wesley %E Adams, John S %X %Z FOR Codes: 111601 111716 %0 Journal Article %~ PubMed %A Mason, R S %T Vitamin D: a hormone for all seasons. %B Climacteric : the journal of the International Menopause Society %D 2011 %C United Kingdom, Irel %I Informa Healthcare %V 14 %N 2 %P 197-203 %@ 1473-0804 %X Vitamin D is principally obtained from skin through the action of ultraviolet B irradiation on 7-dehydrocholesterol. It is further metabolized to 25-hydroxyvitamin D, the major circulating vitamin D compound, and then to 1,25-dihydroxyvitamin D, the hormonal form. The major function of vitamin D compounds is to enhance active absorption of calcium (and phosphate) from the gut, ensuring that bone does not need to be resorbed to maintain blood calcium concentrations despite obligatory urinary losses. Vitamin D compounds have direct effects to enhance bone and muscle function. Based on good evidence, target levels for 25-hydroxyvitamin D in blood are at least 50 nmol/l and there may be a case for higher targets of 75-80 nmol/l. Adequate calcium intakes help to reduce vitamin D degradation. Vitamin D and calcium together reduce the risk of falls and fractures in older people. There are vitamin D receptors in most nucleated cells and preliminary evidence that adequate vitamin D levels may be important in reducing the incidence of, or mortality from, some cancers, and in reducing autoimmune disease. Adequate vitamin D may also allow for a normal innate immune response to pathogens, improve cardiovascular function and mortality, and reduce type 2 diabetes. Supplemental vitamin D seems to work in a generally similar manner to skin-derived vitamin D. %Z FOR Codes: 110306 111603 %0 Journal Article %~ PubMed %A Mason, R S %A Sequeira, V B %A Gordon-Thomson, C %T Vitamin D: the light side of sunshine. %B European journal of clinical nutrition %D 2011 %C United Kingdom, Switzerland %I Nature Publishing Group %V 65 %N 9 %P 986-93 %@ 0954-3007 %X Under normal circumstances, vitamin D is mainly obtained from skin through the action of ultraviolet B irradiation on 7-dehydrocholesterol. It is further metabolized to 25-hydroxyvitamin D (25OHD), the major circulating vitamin D compound, and then to 1,25-dihydroxyvitamin D, the hormonal form. The major function of vitamin D compounds is to enhance active absorption of ingested calcium (and phosphate). This assists in building bone at younger ages and ensures that despite obligatory urinary losses, bone does not need to be resorbed to maintain blood calcium concentrations. Vitamin D compounds appear to have direct effects to improve bone and muscle function, and there is good, although not entirely consistent, evidence that supplemental vitamin D and calcium together reduce falls and fractures in older individuals. On the basis of calcium control and musculoskeletal function, target levels for 25OHD in blood are at least 50-60???nmol/l and there may be a case for higher targets of 75-80???nmol/l. There are vitamin D receptors in most nucleated cells and some evidence, although not consistent, that adequate vitamin D levels may be important in reducing the incidence of, or mortality from, some cancers and in reducing autoimmune disease. Adequate vitamin D may also allow for a normal innate immune response to pathogens, improve cardiovascular function and mortality and increase insulin responsiveness. Vitamin D levels are maintained better in the presence of adequate calcium intakes, more exercise and less obesity. Genetic variation may have an effect on vitamin D blood levels and response to treatment with vitamin D. %Z FOR Codes: 111603 %0 Journal Article %~ PubMed %A Brock, K %A Huang, W-Y %A Fraser, D R %A Ke, L %A Tseng, M %A Stolzenberg-Solomon, R %A U Peters, Z %A Ahn, J %A Purdue, M %A Mason, R S %A McCarty, C %A Ziegler, R %A Graubard, B %T Low vitamin D status is associated with physical inactivity, obesity and low vitamin D intake in a large US sample of healthy middle-aged men and women. %B The Journal of steroid biochemistry and molecular biology %D 2010 %C United Kingdom %I Pergamon %V 121 %N 1-2 %P 462-6 %@ 1879-1220 %X The aim of this study was to investigate modifiable predictors of vitamin D status in healthy individuals, aged 55-74, and living across the USA. Vitamin D status [serum 25-hydroxyvitamin D (25(OH)D)] was measured along with age and season at blood collection, demographics, anthropometry, physical activity (PA), diet, and other lifestyle factors in 1357 male and 1264 female controls selected from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort. Multivariate linear and logistic regression analyses were used to identify associations with vitamin D status. Three%, 29% and 79% of the population had serum 25(OH)D levels<25, <50 and <80 nmol/L, respectively. The major modifiable predictors of low vitamin D status were low vitamin D dietary and supplement intake, body mass index (BMI) >30 kg/m2, physical inactivity (PA) and low milk and calcium supplement intake. In men, 25(OH)D was determined more by milk intake on cereal and in women, by vitamin D and calcium supplement and menopausal hormone therapy (MHT) use. Thus targeting an increase in vigorous activity and vitamin D and calcium intake and decreasing obesity could be public health interventions independent of sun exposure to improve vitamin D status in middle-aged Americans. %Z FOR Codes: 110306 111712 %0 Journal Article %~ PubMed %A Mak, Jenson C S %A Stuart-Harris, Jessica %A Cameron, Ian D %A Mason, Rebecca S %T Oral vitamin D replacement after hip fracture: a comparative review. %B Journal of the American Geriatrics Society %D 2010 %C United States %I Wiley-Blackwell Publishing, Inc. %V 58 %N 2 %P 382-383 %@ 0002-8614 %X %Z FOR Codes: 111199 %0 Journal Article %~ PubMed %A Mason, R S %A Sequeira, V B %A Dixon, K M %A Gordon-Thomson, C %A Pobre, K %A Dilley, A %A Mizwicki, M T %A Norman, A W %A Feldman, D %A Halliday, G M %A Reeve, V E %T PHOTOPROTECTION BY 1alpha,25-DIHYDROXYVITAMIN D AND ANALOGS: FURTHER STUDIES ON MECHANISMS AND IMPLICATIONS FOR UV-DAMAGE. %B The Journal of steroid biochemistry and molecular biology %D 2010 %C United Kingdom %I Pergamon %V 121 %N 1-2 %P 164-8 %@ 1879-1220 %X Ultraviolet (UV) irradiation causes DNA damage in skin cells, immunosuppression and photocarcinogenesis. 1alpha,25-dihydroxyvitamin D3 (1,25D) reduces UV-induced DNA damage in the form of cyclobutane pyrimidine dimers (CPD) in human keratinocytes in culture and in mouse and human skin. UV-induced immunosuppression is also reduced in mice by 1,25D, in part due to the reduction in CPD and a reduction in interleukin (IL-6. The cis-locked analog, 1alpha,25-dihydroxylumisterol3 (JN), which has almost no transactivating activity, reduces UV-induced DNA damage, apoptosis and immunosuppression with similar potency to 1,25D, consistent with a non-genomic signalling mechanism. The mechanism of the reduction in DNA damage in the form of CPD is unclear. 1,25D doubles nuclear expression of p53 compared to UV alone, which suggests that 1,25D facilitates DNA repair. Yet expression of a key DNA repair gene, XPG is not affected by 1,25D. Chemical production of CPD has been described. Incubation of keratinocytes with a nitric oxide donor, SNP, induces CPD in the dark. We previously reported that 1,25D reduced UV-induced nitrite in keratinocytes, similar to aminoguanidine, an inhibitor of nitric oxide synthase. A reduction in reactive nitrogen species has been shown to facilitate DNA repair, but in view of these findings may also reduce CPD formation via a novel mechanism. %Z FOR Codes: 111299 %0 Journal Article %~ PubMed %A Durvasula, Seeta %A Kok, Cindy %A Sambrook, Philip N %A Cumming, Robert G %A Lord, Stephen R %A March, Lynette M %A Mason, Rebecca S %A Seibel, Markus J %A Simpson, Judy M %A Cameron, Ian D %T Sunlight and health: Attitudes of older people living in intermediate care facilities in southern Australia. %B Archives of gerontology and geriatrics %D 2010 %C Ireland %I Elsevier Ireland Ltd %V 51 %N 3 %P e94-9 %@ 1872-6976 %X Older people have a high prevalence of falls and fractures, partly due to vitamin D deficiency. Sunlight is a major source of vitamin D, but many older people living in intermediate care facilities have inadequate sunlight exposure. The aim of this study was to determine the sun exposure practices and attitudes to sunlight in this population. Fifty-seven older residents of intermediate care facilities in Sydney, Australia were interviewed to determine their sun exposure practices, their views on sunlight and health and whether these have changed over their lives, factors affecting sunlight exposure and their knowledge of vitamin D. Sixty percent of the participants preferred to be outdoors, despite more than 92% believing that sunlight was healthy. In their youth however, almost 90% had preferred to be outdoors. Poor health, physical constraints and a sense of lack of ownership of outdoor spaces were barriers to sunlight exposure. Improved physical access, more outdoor leisure activities and promotion of greater autonomy may improve safe and appropriate sunlight exposure in this population. %Z FOR Codes: 111718 %0 Journal Article %~ PubMed %A Damian, Diona L %A Kim, Young Jin %A Dixon, Katie M %A Halliday, Gary M %A Javeri, Arash %A Mason, Rebecca S %T Topical calcitriol protects from UV-induced genetic damage but suppresses cutaneous immunity in humans. %B Experimental dermatology %D 2010 %C United Kingdom, Unit %I Wiley-Blackwell Publishing Ltd. %V 19 %N 8 %P e23-30 %@ 1600-0625 %X Calcitriol, the biologically active form of vitamin D, has been reported to cause both suppressive and protective immune effects in mice. Its immune effects in vivo in humans are unclear. We investigated the in vivo effects of topical calcitriol on minimal erythema dose and skin immune responses in healthy volunteers. We found that calcitriol did not protect from ultraviolet (UV)-induced erythema (sunburn) when applied either 24 h before or immediately after irradiation, although it decreased the density of sunburn cells and thymine dimers seen on biopsy when applied 24 h before and again immediately after irradiation. Using the Mantoux reaction as a model of skin immunity, we found that topical calcitriol applied at high total doses reduced the Mantoux responses of nearby untreated, unirradiated skin, suggesting a para-local or systemic immunosuppressive effect not observed with lower calcitriol doses. We then measured UV-induced suppression of Mantoux reactions at vehicle-treated sites and sites treated with low-dose calcitriol, and found that calcitriol neither reduced nor enhanced UV-induced immunosuppression. Despite calcitriol reducing UV-induced DNA damage, which should protect the immune system, it has immunosuppressive effects in our model which may help to explain the efficacy of analogues such as calcipotriol in the treatment of psoriasis. %Z FOR Codes: 111299 %0 Journal Article %~ PubMed %A Dixon, Katie M %A Sequeira, Vanessa B %A Camp, Aaron J %A Mason, Rebecca S %T Vitamin D-fence. %B Photochemical & Photobiological Sciences %D 2010 %C United Kingdom, Swit %I Royal Society of Chemistry %V 9 %N 4 %P 564-70 %@ 1474-9092 %X The role of vitamin D in the immune system is complex. Vitamin D is produced in the skin following exposure to ultraviolet radiation. There is compelling evidence that vitamin D compounds protect against ultraviolet radiation-induced DNA damage and immune suppression, suggesting it may be beneficial as a skin cancer preventive agent. However, vitamin D has many modulatory effects on the immune system and it has in fact been suggested that the immune suppression generally attributed to the UVB portion of sunlight is mediated through vitamin D. Here we describe the role of vitamin D compounds as "defence" molecules against UVR-induced damage, and investigate both sides of the "fence" regarding the effects of vitamin D compounds and the immune system. %Z FOR Codes: 110306 111299 %0 Journal Article %~ PubMed %A Huang, H H %A Brennan, T C %A Muir, M M %A Mason, R S %T Functional alpha1- and beta2-adrenergic receptors in human osteoblasts. %B Journal of cellular physiology %D 2009 %C United States %I John Wiley & Sons %V 220 %N 1 %P 267-275 %@ 1097-4652 %X Central (hypothalamic) control of bone mass is proposed to be mediated through beta2-adrenergic receptors (beta2-ARs). While investigations in mouse bone cells suggest that epinephrine enhances both RANKL and OPG mRNA via both beta-ARs and alpha-ARs, whether alpha-ARs are expressed in human bone cells is controversial. The current study investigated the expression of alpha1-AR and beta2-AR mRNA and protein and the functional role of adrenergic stimulation in human osteoblasts (HOBs). Expression of alpha1B- and beta2-ARs was examined by RT-PCR, immunofluorescence microscopy and Western blot (for alpha1B-ARs). Proliferation in HOBs was assessed by (3)H-thymidine incorporation and expression of RANKL and OPG was determined by quantitative RT-PCR. RNA message for alpha1B- and beta2-ARs was expressed in HOBs and MG63 human osteosarcoma cells. alpha1B- and beta2-AR immunofluorescent localization in HOBs was shown for the first time by deconvolution microscopy. alpha1B-AR protein was identified in HOBs by Western blot. Both alpha1-agonists and propranolol (beta-blocker) increased HOB replication but fenoterol, a beta2-agonist, inhibited it. Fenoterol nearly doubled RANKL mRNA and this was inhibited by propranolol. The alpha1-agonist cirazoline increased OPG mRNA and this increase was abolished by siRNA knockdown of alpha1B-ARs in HOBs. These data indicate that both alpha1-ARs and beta2-ARs are present and functional in HOBs. In addition to beta2-ARs, alpha1-ARs in human bone cells may play a role in modulation of bone turnover by the sympathetic nervous system. %Z FOR Codes: 110199 %0 Journal Article %~ PubMed %A Brennan, Tc %A Rybchyn, Ms %A Green, W %A Atwa, S %A Conigrave, Ad %A Mason, Rs %T Osteoblasts play key roles in the mechanisms of action of strontium ranelate. %B British journal of pharmacology %D 2009 %C United Kingdom %I John Wiley & Sons Ltd. %V 157 %N 7 %P 1291-300 %@ 0007-1188 %X Strontium ranelate reduces fracture risk in postmenopausal women with osteoporosis. Evidence from non-clinical studies and analyses of bone markers in phase III trials indicate that this is due to an increase in osteoblast formation and a decrease of osteoclastic resorption. The aim of this work was to investigate, in human cells, the mechanisms by which strontium ranelate is able to influence the activities of osteoblasts and osteoclasts. %Z FOR Codes: 111502 %0 Journal Article %A Sequeira, V B %A Dixon, Katie %A Mason, Rebecca %T Resisting the sun with Vitamin D %B Immunology, Endocrine and Metabolic Agents in Medicinal Chemistry %D 2009 %C Netherlands %I Benthem Science %V 9 %N %P 126-136 %@ 1871-5222 %X %Z FOR Codes: 110701 %0 Journal Article %A Diamond, Terry %A Mason, Rebecca %T Understanding the importance of vitamin D for bone and systemic health %B Medicine Today %D 2009 %C Australia %I Medicine Today %V 10 %N %P 1 %@ 1443-430X %X %Z FOR Codes: 110199 %0 Journal Article %~ PubMed %A McCombie, Anna-Marie %A Mason, Rebecca S %A Damian, Diona L %T Vitamin D deficiency in Sydney skin cancer patients. %B The Medical Journal of Australia %D 2009 %C Australia %I Australasian Medical Publishing Company Pty. Ltd %V 190 %N 2 %P 102 %@ 1326-5377 %X %Z FOR Codes: 111104 %0 Journal Article %~ PubMed %A Dixon, Katie M %A Mason, Rebecca S %T Vitamin D. %B The international journal of biochemistry & cell biology %D 2009 %C United Kingdom %I Pergamon %V 41 %N 0 %P 982-5 %@ 1357-2725 %X The primary source of vitamin D is the skin, following exposure to ultraviolet radiation. Vitamin D is well known for its effects on stimulating calcium absorption and is thus essential for maintenance of normal bone. It is also important for muscle function and has more recently been implicated in protection against several diseases including diabetes. Different pathways of action have been described for vitamin D compounds and various analogs specific to these pathways have demonstrated potential for therapeutic use. Recent studies suggest a novel role for vitamin D compounds in protection against cancer, a proposal supported by substantial epidemiological evidence. %Z FOR Codes: 111603 %0 Journal Article %~ PubMed %A Javeri, Arash %A Huang, Xiao Xuan %A Bernerd, Françoise %A Mason, Rebecca S %A Halliday, Gary M %T Human 8-oxoguanine-DNA glycosylase 1 protein and gene are expressed more abundantly in the superficial than basal layer of human epidermis. %B DNA repair %D 2008 %C Netherlands %I Elsevier BV %V 7 %N 9 %P 1542-50 %@ 1568-7864 %X Human 8-oxoguanine-DNA glycosylase 1 (hOGG1) repairs 8-oxo-7,8-dihydro-2''-deoxyguanosine (8-oxo-dG) which results from oxidation of guanine. Reactive oxygen species (ROS) formed in response to ultraviolet (UV) radiation cause this DNA damage, which is involved in pathological processes such as carcinogenesis and aging. The initiation of skin tumors probably requires penetration of UV to the actively dividing basal layer of the epidermis in order for acute damage to become fixed as mutations. Previously, the majority of UVB fingerprint mutations have been found in the upper layers of human skin tumors, while UVA mutations have been found mostly in the lower layer. Our aim was to determine whether this localization of UVA-induced DNA damage is related to stratification of the repair-enzyme hOGG1. Anti-hOGG1 immunohistochemical staining of frozen sections of human foreskin, adult buttock skin, and reconstructed human skin samples showed the highest expression of hOGG1 in the superficial epidermal layer (stratum granulosum). Study of the hOGG1 mRNA expression again showed the highest level in the upper region of the epidermis. This was not regulated by UV irradiation but by the differentiation state of keratinocytes as calcium-induced differentiation increased hOGG1 gene expression. UVA-induced 8-oxo-dG was repaired more rapidly in the upper layer of human skin compared to the lower layers. Our results indicate that weaker expression of the nuclear form of hOGG1 enzyme in the basal cells of the epidermis may lead to a lack of DNA repair in these cells and therefore accumulation of UVA-induced oxidative DNA mutations. %Z FOR Codes: 110304 %0 Journal Article %A Sanchez Riera, Lidia %A Wilson, Nicholas M %A Sambrook, Philip %A Kok, Cindy %A Cumming, Robert %A Cameron, Ian %A Chen, Jian Sheng %A Simpson, Judy %A Mason, Rebecca %A Seibel, Markus %A March, Lyn %T Trends in calcium and vitamin D usage among older people in nursing care facilities in Australia: still falling short of the guidelines %B International Journal of Rheumatic Diseases %D 2008 %C Australia %I Wiley-Blackwell %V 11 %N %P 430-434 %@ 1756-1841 %X %Z FOR Codes: 110322 111702 %0 Journal Article %~ PubMed %A Lee, Heather J %A Mun, Hee-Chang %A Lewis, Narelle C %A Crouch, Michael F %A Culverston, Emma L %A Mason, Rebecca S %A Conigrave, Arthur D %T Allosteric activation of the extracellular Ca2+-sensing receptor by L-amino acids enhances ERK1/2 phosphorylation. %B The Biochemical journal %D 2007 %C United Kingdom %I Portland Press Ltd. %V 404 %N 1 %P 141-149 %@ 1470-8728 %X The calcium-sensing receptor (CaR) mediates feedback control of Ca2+o (extracellular Ca2+) concentration. Although the mechanisms are not fully understood, the CaR couples to several important intracellular signalling enzymes, including PI-PLC (phosphoinositide-specific phospholipase C), leading to Ca2+i (intracellular Ca2+) mobilization, and ERK1/2 (extracellular-signal-regulated kinase 1/2). In addition to Ca2+o, the CaR is activated allosterically by several subclasses of L-amino acids, including the aromatics L-phenylalanine and L-tryptophan. These amino acids enhance the Ca2+o-sensitivity of Ca2+i mobilization in CaR-expressing HEK-293 (human embryonic kidney) cells and normal human parathyroid cells. Furthermore, on a background of a physiological fasting serum L-amino acid mixture, they induce a small, but physiologically significant, enhancement of Ca2+o-dependent suppression of PTH (parathyroid hormone) secretion. The impact of amino acids on CaR-stimulated ERK1/2, however, has not been determined. In the present study, we examined the effects of L-amino acids on Ca2+o-stimulated ERK1/2 phosphorylation as determined by Western blotting and a newly developed quantitative assay (SureFire). L-Amino acids induced a small, but significant, enhancement of Ca2+o-stimulated ERK1/2. In CaR-expressing HEK-293 cells, 10 mM L-phenylalanine lowered the EC50 for Ca2+o from approx. 2.3 to 2.0 mM in the Western blot assay and from 3.4 to 2.9 mM in the SureFire assay. The effect was stereoselective (L>D), and another aromatic amino acid, L-tryptophan, was also effective. The effects of amino acids were investigated further in HEK-293 cells that expressed the CaR mutant S169T. L-Phenylalanine normalized the EC50 for Ca2+o-stimulated Ca2+i mobilization from approx. 12 mM to 5.0 mM and ERK1/2 phosphorylation from approx. 4.6 mM to 2.6 mM. Taken together, the data indicate that L-phenylalanine and other amino acids enhance the Ca2+o-sensitivity of CaR-stimulated ERK1/2 phosphorylation; however, the effect is comparatively small and operates in the form of a fine-tuning mechanism. %Z FOR Codes: %0 Journal Article %~ PubMed %A Brock, K %A Cant, R %A Clemson, L %A Mason, R S %A Fraser, D R %T Effects of diet and exercise on plasma vitamin D (25(OH)D) levels in Vietnamese immigrant elderly in Sydney, Australia. %B The Journal of steroid biochemistry and molecular biology %D 2007 %C United Kingdom %I Pergamon %V 103 %N 3-5 %P 786-792 %@ 0960-0760 %X Vitamin D deficiency may be associated with osteoporosis and fractures in the elderly. In Australia where there is a sizeable Vietnamese population, research has not yet clarified the roles of diet, exercise and sun exposure in determining vitamin D status. Plasma samples for 25-hydroxy-vitamin D (25(OH)D); dietary intake of vitamin D and calcium; muscle strength and sun exposure were measured and weekly dairy intake, exercise levels and smoking habits were surveyed in free-living elderly of Vietnamese and Australian/British origin. There was marginal vitamin D deficiency (<37 nmol/L 25(OH)D) in 63% of Vietnamese but only in 37% of Australian/British born. Low dairy intake and no vigorous exercise were best predictors of vitamin D deficiency in Vietnamese, taking into account age, gender, dietary intake and sun exposure. Since these migrant elderly may not get adequate sun exposure due to either clothing customs or cultural norms that encourage fair (untanned) skin, it is important to encourage increased exercise and dairy intake. %Z FOR Codes: %0 Journal Article %~ PubMed %A Rohanizadeh, Ramin %A Swain, Michael %A Mason, Rebecca %T Gelatin sponges (Gelfoam( (R) )) as a scaffold for osteoblasts. %B Journal of materials science. Materials in medicine %D 2007 %C United States %I Springer New York LLC %V 19 %N 0 %P 1173-82 %@ 0957-4530 %X Gelatine sponge because of its flexibility, biocompatibility, and biodegradability, has the potential to be used as a scaffold to support osteoblasts and to promote bone regeneration in defective areas. This study aimed to determine osteoblast proliferation, differentiation, and integration in modified and un-modified gelatine sponges. Three scaffolds were studied: gelatine sponge (Gelfoam), gelatin sponge/mineral (hydroxyapatite) composite, and gelatin sponge/polymer (poly-lactide-co-glycolide) composite. 2-D plastic coverslip was used as control. The gelatin sponges were modified using PLGA coating and mineral deposition to increase biodegradation resistance and osteoblast proliferation respectively. The scaffolds were characterized using Scanning Electron Microscopy (SEM) and X-ray diffraction. Cell number (DNA content), cell-replication rate (thymidine assay), and cell differentiation (alkaline phosphatase activity) were measured 24 h, 3 days, and 1, 2, 3 weeks after the osteoblast-like cells were cultured onto the scaffolds. Cell penetration into the sponges was determined using haematoxylin-eosin staining. Both modified and unmodified gelatine sponges demonstrated ability to support cell growth and cells were able to penetrate into the sponge pores. In a comparison of different scaffolds, cell number and cell replication were highest in sponge/hydroxyapatite composite and lowest in sponge/PLGA composite. %Z FOR Codes: 111699 %0 Journal Article %~ PubMed %A Dixon, K M %A Deo, S S %A Norman, A W %A Bishop, J E %A Halliday, G M %A Reeve, V E %A Mason, R S %T In vivo relevance for photoprotection by the vitamin D rapid response pathway. %B The Journal of steroid biochemistry and molecular biology %D 2007 %C United Kingdom %I Pergamon %V 103 %N 3-5 %P 451-456 %@ 0960-0760 %X Vitamin D is produced by exposure of 7-dehydrocholesterol in the skin to UV irradiation (UVR) and further converted in the skin to the biologically active metabolite, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and other compounds. UVR also results in DNA damage producing cyclobutane pyrimidine dimers (CPD). We previously reported that 1,25(OH)(2)D(3) at picomolar concentrations, protects human skin cells from UVR-induced apoptosis, and decreases CPD in surviving cells. 1,25(OH)(2)D(3) has been shown to generate biological responses via two pathways-the classical steroid receptor/genomic pathway or a rapid, non-genomic pathway mediated by a putative membrane receptor. Whether the rapid response pathway is physiologically relevant is unclear. A cis-locked, rapid-acting agonist 1,25(OH)(2)lumisterol(3) (JN), entirely mimicked the actions of 1,25(OH)(2)D(3) to reduce fibroblast and keratinocyte loss and CPD damage after UVR. The effects of 1,25(OH)(2)D(3) were abolished by a rapid-acting antagonist, but not by a genomic antagonist. Skh:hr1 mice exposed to three times the minimal erythemal dose of solar-simulated UVR and treated topically with 1,25(OH)(2)D(3) or JN immediately after UVR showed reduction in UVR-induced UVR-induced sunburn cells (p<0.01 and <0.05, respectively), CPD (p<0.01 for both) and immunosuppression (p<0.001 for both) compared with vehicle-treated mice. These results show for the first time an in vivo biological response mediated by a rapid-acting analog of the vitamin D system. The data support the hypothesis that 1,25(OH)(2)D(3) exerts its photoprotective effects via the rapid pathway and raise the possibility that other D compounds produced in skin may contribute to the photoprotective effects. %Z FOR Codes: 111603 %0 Journal Article %~ Isi %A Brennan, TC %A Rybchyn, MS %A Halbout, P %A Conigrave, AD %A Mason, RS %T Strontium ranelate effects in human osteoblasts support its uncoupling effect on bone formation and bone resorption %B CALCIFIED TISSUE INTERNATIONAL %D 2007 %C United States %I Springer %V 80 %N 0 %P S72-S73 %@ 0171-967X %X %Z FOR Codes: %0 Journal Article %~ Isi %A Brennan, TC %A Rybchyn, MS %A Conigrave, AD %A Mason, RS %T Strontium ranelate effects on bone formation and bone resorption: an in vitro in human osteoblasts %B OSTEOPOROSIS INTERNATIONAL %D 2007 %C United Kingdom %I Springer UK %V 18 %N Supp 1 %P S166-S167 %@ %X %Z FOR Codes: %0 Journal Article %~ PubMed %A Gorman, Shelley %A Kuritzky, L Alexandra %A Judge, Melinda A %A Dixon, Katie M %A McGlade, Jacqueline P %A Mason, Rebecca S %A Finlay-Jones, John J %A Hart, Prue H %T Topically applied 1,25-dihydroxyvitamin D3 enhances the suppressive activity of CD4+CD25+ cells in the draining lymph nodes. %B Journal of immunology %D 2007 %C United States %I American Association of Immunologists %V 179 %N 9 %P 6273-6283 %@ 0022-1767 %X The immunomodulatory effects of vitamin D have been described following chronic oral administration to mice or supplementation of cell cultures with 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the active form of vitamin D. In this study, topically applied 1,25(OH)(2)D(3), enhanced the suppressive capacity of CD4(+)CD25(+) cells from the draining lymph nodes. The effects of topical 1,25(OH)(2)D(3) were compared with those of UVB irradiation, which is the environmental factor required for 1,25(OH)(2)D(3) production in skin. CD4(+) cells from the skin-draining lymph nodes (SDLN) of either 1,25(OH)(2)D(3)-treated or UVB-irradiated mice had reduced capacity to proliferate to Ags presented in vitro, and could suppress Ag-specific immune responses upon adoptive transfer into naive mice. This regulation was lost upon removal of CD4(+)CD25(+) cells. Furthermore, purified CD4(+)CD25(+) cells from the SDLN of 1,25(OH)(2)D(3)-treated or UVB-irradiated mice compared with equal numbers of CD4(+)CD25(+) cells from control mice had increased capacity to suppress immune responses in both in vitro and in vivo assay systems. Following the sensitization of recipient mice with OVA, the proportion of CD4(+)Foxp3(+) cells of donor origin significantly increased in recipients of CD4(+)CD25(+) cells from the SDLN of 1,25(OH)(2)D(3)-treated mice, indicating that these regulatory T cells can expand in vivo with antigenic stimulation. These studies suggest that 1,25(OH)(2)D(3) may be an important mediator by which UVB-irradiation exerts some of its immunomodulatory effects. %Z FOR Codes: 111699