{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T07:55:28Z","timestamp":1793692528242,"version":"4.5.1"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,9,11]],"date-time":"2017-09-11T00:00:00Z","timestamp":1505088000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,9,11]],"date-time":"2017-09-11T00:00:00Z","timestamp":1505088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Increasing evidence regarding positive effects of exposure to sunlight has led to suggestions that current advice may be overly weighted in favour of avoidance. UV-A has been reported to lower blood pressure, possibly through nitric oxide (NO) production in skin. Here, we set out to investigate effects of UV-A and solar-simulated radiation on the potential source of dermal NO, the effective doses and wavelengths, the responsiveness of different human skin cells, the magnitude of inter-individual differences and the potential influence of age. We utilised isogenic keratinocytes, microvascular endothelial cells, melanocytes and fibroblasts isolated from 36 human skins ranging from neonates to 86 years old. We show that keratinocytes and microvascular endothelial cells show greatest NO release following biologically relevant doses of UV-A. This was consistent across multiple neonatal donors and the effect is maintained in adult keratinocytes. Our observations are consistent with a bi-phasic mechanism by which UV-A can trigger vasodilatory effects. Analyses of NO-production spectra adds further evidence that nitrites in skin cells are the source of UV-mediated NO release. These potentially positive effects of ultraviolet radiation lend support for objective assessment of environmental influence on human health and the idea of \u201chealthy sun exposure\u201d.<\/jats:p>","DOI":"10.1038\/s41598-017-11567-5","type":"journal-article","created":{"date-parts":[[2017,9,5]],"date-time":"2017-09-05T10:15:59Z","timestamp":1504606559000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Ultraviolet Radiation-Induced Production of Nitric Oxide:A multi-cell and multi-donor analysis"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2097-530X","authenticated-orcid":false,"given":"Graham","family":"Holliman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Lowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3304-0490","authenticated-orcid":false,"given":"Sarah","family":"Felton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Raj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,9,11]]},"reference":[{"key":"11567_CR1","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1111\/1523-1747.ep12479237","volume":"77","author":"MF Holick","year":"1981","unstructured":"Holick, M. F. The Cutaneous Photosynthesis of Previtamin D3: A Unique Photoendocrine System. Journal of Investigative Dermatology \n                           77, 51\u201358, doi:https:\/\/doi.org\/10.1111\/1523-1747.ep12479237 (1981).","journal-title":"Journal of Investigative Dermatology"},{"key":"11567_CR2","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1126\/science.6281884","volume":"216","author":"JA MacLaughlin","year":"1982","unstructured":"MacLaughlin, J. A., Anderson, R. R. & Holick, M. F. Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin. Science \n                           216, 1001\u20131003 (1982).","journal-title":"Science"},{"key":"11567_CR3","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1093\/eurheartj\/ehq069","volume":"31","author":"M Feelisch","year":"2010","unstructured":"Feelisch, M. et al. Is sunlight good for our heart? European heart journal \n                           31, 1041\u20131045, doi:https:\/\/doi.org\/10.1093\/eurheartj\/ehq069 (2010).","journal-title":"European heart journal"},{"key":"11567_CR4","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1097\/MNH.0000000000000188","volume":"25","author":"RS Johnson","year":"2016","unstructured":"Johnson, R. S., Titze, J. & Weller, R. Cutaneous control of blood pressure. Current Opinion in Nephrology and Hypertension \n                           25, 11\u201315, doi:https:\/\/doi.org\/10.1097\/mnh.0000000000000188 (2016).","journal-title":"Current Opinion in Nephrology and Hypertension"},{"key":"11567_CR5","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1038\/jid.2014.27","volume":"134","author":"D Liu","year":"2014","unstructured":"Liu, D. et al. UVA irradiation of human skin vasodilates arterial vasculature and lowers blood pressure independently of nitric oxide synthase. J Invest Dermatol \n                           134, 1839\u20131846, doi:https:\/\/doi.org\/10.1038\/jid.2014.27 (2014).","journal-title":"J Invest Dermatol"},{"key":"11567_CR6","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1159\/000441266","volume":"41","author":"RB Weller","year":"2016","unstructured":"Weller, R. B. Sunlight Has Cardiovascular Benefits Independently of Vitamin D. Blood Purification \n                           41, 130\u2013134 (2016).","journal-title":"Blood Purification"},{"key":"11567_CR7","doi-asserted-by":"publisher","unstructured":"Weller, R. B. The health benefits of UV radiation exposure through vitamin D production or non-vitamin D pathways. Blood pressure and cardiovascular disease. Photochemical & photobiological sciences: Official journal of the European Photochemistry Association and the European Society for Photobiology, doi:https:\/\/doi.org\/10.1039\/c6pp00336b (2016).","DOI":"10.1039\/c6pp00336b"},{"key":"11567_CR8","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1161\/CIRCRESAHA.109.207019","volume":"105","author":"C Opl\u00e4nder","year":"2009","unstructured":"Opl\u00e4nder, C. et al. Whole Body UVA Irradiation Lowers Systemic Blood Pressure by Release of Nitric Oxide From Intracutaneous Photolabile Nitric Oxide Derivates. Circulation Research \n                           105, 1031\u20131040, doi:https:\/\/doi.org\/10.1161\/circresaha.109.207019 (2009).","journal-title":"Circulation Research"},{"key":"11567_CR9","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1042\/bj3570593","volume":"357","author":"WK Alderton","year":"2001","unstructured":"Alderton, W. K., Cooper, C. E. & Knowles, R. G. Nitric oxide synthases: structure, function and inhibition. The Biochemical journal \n                           357, 593\u2013615 (2001).","journal-title":"The Biochemical journal"},{"key":"11567_CR10","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.freeradbiomed.2007.04.026","volume":"43","author":"NS Bryan","year":"2007","unstructured":"Bryan, N. S. & Grisham, M. B. Methods to detect nitric oxide and its metabolites in biological samples. Free radical biology & medicine \n                           43, 645\u2013657, doi:https:\/\/doi.org\/10.1016\/j.freeradbiomed.2007.04.026 (2007).","journal-title":"Free radical biology & medicine"},{"key":"11567_CR11","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.freeradbiomed.2006.05.019","volume":"41","author":"NS Bryan","year":"2006","unstructured":"Bryan, N. S. Nitrite in nitric oxide biology: cause or consequence? A systems-based review. Free radical biology & medicine \n                           41, 691\u2013701, doi:https:\/\/doi.org\/10.1016\/j.freeradbiomed.2006.05.019 (2006).","journal-title":"Free radical biology & medicine"},{"key":"11567_CR12","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.freeradbiomed.2004.04.027","volume":"37","author":"JO Lundberg","year":"2004","unstructured":"Lundberg, J. O. & Govoni, M. Inorganic nitrate is a possible source for systemic generation of nitric oxide. Free Radical Biology and Medicine \n                           37, 395\u2013400, doi:https:\/\/doi.org\/10.1016\/j.freeradbiomed.2004.04.027 (2004).","journal-title":"Free Radical Biology and Medicine"},{"key":"11567_CR13","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.bbrc.2010.02.136","volume":"396","author":"JO Lundberg","year":"2010","unstructured":"Lundberg, J. O. & Weitzberg, E. NO-synthase independent NO generation in mammals. Biochem Biophys Res Commun \n                           396, 39\u201345, doi:https:\/\/doi.org\/10.1016\/j.bbrc.2010.02.136 (2010).","journal-title":"Biochem Biophys Res Commun"},{"key":"11567_CR14","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1002\/med.20151","volume":"29","author":"EE van Faassen","year":"2009","unstructured":"van Faassen, E. E. et al. Nitrite as regulator of hypoxic signaling in mammalian physiology. Medicinal research reviews \n                           29, 683\u2013741, doi:https:\/\/doi.org\/10.1002\/med.20151 (2009).","journal-title":"Medicinal research reviews"},{"key":"11567_CR15","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1073\/pnas.0234600100","volume":"100","author":"J Rodriguez","year":"2003","unstructured":"Rodriguez, J., Maloney, R. E., Rassaf, T., Bryan, N. S. & Feelisch, M. Chemical nature of nitric oxide storage forms in rat vascular tissue. Proceedings of the National Academy of Sciences \n                           100, 336\u2013341, doi:https:\/\/doi.org\/10.1073\/pnas.0234600100 (2003).","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"11567_CR16","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.niox.2009.10.006","volume":"22","author":"CV Suschek","year":"2010","unstructured":"Suschek, C. V., Oplander, C. & van Faassen, E. E. Non-enzymatic NO production in human skin: effect of UVA on cutaneous NO stores. Nitric Oxide \n                           22, 120\u2013135, doi:https:\/\/doi.org\/10.1016\/j.niox.2009.10.006 (2010).","journal-title":"Nitric Oxide"},{"key":"11567_CR17","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/jid.2008.296","volume":"129","author":"M Mowbray","year":"2009","unstructured":"Mowbray, M. et al. Enzyme-Independent NO Stores in Human Skin: Quantification and Influence of UV Radiation. J Invest Dermatol \n                           129, 834\u2013842 (2009).","journal-title":"J Invest Dermatol"},{"key":"11567_CR18","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.freeradbiomed.2003.11.011","volume":"36","author":"T Rassaf","year":"2004","unstructured":"Rassaf, T., Feelisch, M. & Kelm, M. Circulating NO pool: assessment of nitrite and nitroso species in blood and tissues. Free Radical Biology and Medicine \n                           36, 413\u2013422, doi:https:\/\/doi.org\/10.1016\/j.freeradbiomed.2003.11.011 (2004).","journal-title":"Free Radical Biology and Medicine"},{"key":"11567_CR19","doi-asserted-by":"publisher","first-page":"109","DOI":"10.4161\/derm.20013","volume":"4","author":"A Juzeniene","year":"2012","unstructured":"Juzeniene, A. & Moan, J. Beneficial effects of UV radiation other than via vitamin D production. 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Nitric oxide function in the skin. Nitric Oxide \n                           10, 179\u2013193, doi:https:\/\/doi.org\/10.1016\/j.niox.2004.04.005 (2004).","journal-title":"Nitric Oxide"},{"key":"11567_CR24","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1111\/j.1476-5381.1995.tb13341.x","volume":"114","author":"G Deliconstantinos","year":"1995","unstructured":"Deliconstantinos, G., Villiotou, V. & Stravrides, J. C. Release by ultraviolet B (u.v.B) radiation of nitric oxide (NO) from human keratinocytes: a potential role for nitric oxide in erythema production. British journal of pharmacology \n                           114, 1257\u20131265 (1995).","journal-title":"British journal of pharmacology"},{"key":"11567_CR25","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1046\/j.1523-1747.1998.00253.x","volume":"111","author":"A Kuhn","year":"1998","unstructured":"Kuhn, A. et al. Aberrant timing in epidermal expression of inducible nitric oxide synthase after UV irradiation in cutaneous lupus erythematosus. J Invest Dermatol \n                           111, 149\u2013153, doi:https:\/\/doi.org\/10.1046\/j.1523-1747.1998.00253.x (1998).","journal-title":"J Invest Dermatol"},{"key":"11567_CR26","doi-asserted-by":"publisher","first-page":"4954","DOI":"10.1073\/pnas.0401141101","volume":"101","author":"NS Agar","year":"2004","unstructured":"Agar, N. S. et al. The basal layer in human squamous tumors harbors more UVA than UVB fingerprint mutations: A role for UVA in human skin carcinogenesis. Proceedings of the National Academy of Sciences of the United States of America \n                           101, 4954\u20134959, doi:https:\/\/doi.org\/10.1073\/pnas.0401141101 (2004).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"11567_CR27","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1046\/j.1523-1747.1999.00610.x","volume":"112","author":"DL Damian","year":"1999","unstructured":"Damian, D. L., Barnetson, R. S. C. & Halliday, G. M. Low-Dose UVA and UVB have Different Time Courses for Suppression of Contact Hypersensitivity to a Recall Antigen in Humans. Journal of Investigative Dermatology \n                           112, 939\u2013944, doi:https:\/\/doi.org\/10.1046\/j.1523-1747.1999.00610.x (1999).","journal-title":"Journal of Investigative Dermatology"},{"key":"11567_CR28","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.dnarep.2016.05.024","volume":"44","author":"P Karran","year":"2016","unstructured":"Karran, P. & Brem, R. Protein oxidation, UVA and human DNA repair. DNA Repair \n                           44, 178\u2013185, doi:https:\/\/doi.org\/10.1016\/j.dnarep.2016.05.024 (2016).","journal-title":"DNA Repair"},{"key":"11567_CR29","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1093\/ije\/dyt168","volume":"42","author":"P Brondum-Jacobsen","year":"2013","unstructured":"Brondum-Jacobsen, P., Nordestgaard, B. G., Nielsen, S. F. & Benn, M. Skin cancer as a marker of sun exposure associates with myocardial infarction, hip fracture and death from any cause. 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UVA\/B-Induced Apoptosis in Human Melanocytes Involves Translocation of Cathepsins and Bcl-2 Family Members. Journal of Investigative Dermatology \n                           126, 1119\u20131127, doi:https:\/\/doi.org\/10.1038\/sj.jid.5700124 (2006).","journal-title":"Journal of Investigative Dermatology"},{"key":"11567_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/srep27890","volume":"6","author":"P Waster","year":"2016","unstructured":"Waster, P., Eriksson, I., Vainikka, L., Rosdahl, I. & Ollinger, K. Extracellular vesicles are transferred from melanocytes to keratinocytes after UVA irradiation. Scientific reports \n                           6, 27890, doi:https:\/\/doi.org\/10.1038\/srep27890 (2016).","journal-title":"Scientific reports"},{"key":"11567_CR34","doi-asserted-by":"publisher","DOI":"10.1117\/1.2957970","volume":"13","author":"M Meinhardt","year":"2008","unstructured":"Meinhardt, M., Krebs, R., Anders, A., Heinrich, U. & Tronnier, H. 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