{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T06:11:19Z","timestamp":1783663879377,"version":"3.55.0"},"reference-count":23,"publisher":"Wiley","issue":"S2","license":[{"start":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:00:00Z","timestamp":1703030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hyperpigmented spots are common issues in all ethnicities with a hallmark characteristic of increased melanocyte dendricity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To determine (1) potential receptors and\/or cytokines that are involved in increased melanocyte dendricity in multiple facial spot types; (2) treatment effects of skin\u2010lightening compounds on identified cytokine release from keratinocytes and on dendricity in melanocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Facial spots (melasma, solar lentigo, acne\u2010induced post\u2010inflammatory hyperpigmentation) and adjacent non\u2010spot skin biopsies were collected from Chinese women (age 20\u201370). The epidermal supra and basal layers were laser dissected to enrich keratinocyte or melanocyte biology respectively for transcriptome analysis. Melanocyte dendricity was assessed histologically by immunofluorescent staining. Effect of interleukin\u20106 (IL\u20106) and endothelin\u20101 (ET\u20101) on melanocyte dendricity and melanosome transfer were assessed in human melanocytes or melanocyte\u2010keratinocyte co\u2010culture models. Treatment effects of skin\u2010lightening compounds (niacinamide, tranexamic acid [TxA], sucrose laurate\/dilaurate mixture [SDL]) were assessed on IL\u20106 or ET\u20101 release from keratinocytes and on dendricity in melanocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Transcriptome analysis revealed IL\u20106 receptor and ET\u20101 receptor were significantly upregulated compared to the adjacent normal skin, visually confirmed at the protein level through immunostaining. Melanocytes in spot areas are more dendritic than melanocytes in adjacent non\u2010spot skin. The addition of IL\u20106 and ET\u20101 to cell culture models increased melanocyte dendricity and melanosome transfer. IL\u20106 release was significantly suppressed by niacinamide and its combination, while ET\u20101 release was significantly reduced by both niacinamide and TxA. In contrast, SDL acted directly upon melanocytes to reduce dendricity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Interleukin\u20106 and ET\u20101 receptors are significantly upregulated in multiple facial spot types. The <jats:italic>in\u00a0vitro<\/jats:italic> testing demonstrated their respective ligands increased melanocyte dendricity. Tested skin\u2010lightening compounds showed reduction in release of IL\u20106\/ET\u20101 from epidermal keratinocytes and\/or inhibition of melanocyte dendricity. This work sheds light on pathophysiological mechanism of facial spots and potential new mechanisms of these skin\u2010lightening compounds which warrant further human clinical validation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.19719","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T09:50:45Z","timestamp":1703065845000},"page":"3-10","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Role of interleukin\u20106 and endothelin\u20101 receptors in enhanced melanocyte dendricity of facial spots and suppression of their ligands by niacinamide and tranexamic acid"],"prefix":"10.1111","volume":"38","author":[{"given":"T.","family":"Hakozaki","sequence":"first","affiliation":[{"name":"The Procter &amp; Gamble Company, Mason Business Center  Mason Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Wang","sequence":"additional","affiliation":[{"name":"The Procter &amp; Gamble Company, Mason Business Center  Mason Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Laughlin","sequence":"additional","affiliation":[{"name":"The Procter &amp; Gamble Company, Mason Business Center  Mason Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Jarrold","sequence":"additional","affiliation":[{"name":"The Procter &amp; Gamble Company, Mason Business Center  Mason Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Procter &amp; Gamble Company, Mason Business Center  Mason Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Furue","sequence":"additional","affiliation":[{"name":"Department of Dermatology Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ski2.96"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0b013e3181cd4396"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2009.01057.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jmicro\/dfaa054"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.17846"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.2002.04834.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1011-1344(98)00212-7"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041330111"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12709595"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.115.3.821"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12325522"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1998.00272.x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb08679.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700180"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.15651"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2005.06966.x"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2015.179"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20153666"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.103871"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/ced.12874"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-017-0263-3"},{"issue":"8","key":"e_1_2_9_23_1","first-page":"753","article-title":"Topical tranexamic acid as a promising treatment for melasma","volume":"19","author":"Ebrahimi B","year":"2014","journal-title":"J Res Med Sci"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13555-022-00779-x"}],"container-title":["Journal of the European Academy of Dermatology and Venereology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdv.19719","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T09:42:46Z","timestamp":1704361366000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jdv.19719"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,20]]},"references-count":23,"journal-issue":{"issue":"S2","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1111\/jdv.19719"],"URL":"https:\/\/doi.org\/10.1111\/jdv.19719","archive":["Portico"],"relation":{},"ISSN":["0926-9959","1468-3083"],"issn-type":[{"value":"0926-9959","type":"print"},{"value":"1468-3083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,20]]},"assertion":[{"value":"2023-09-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}