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Our previous studies demonstrated that cutaneous pigmentation could promote skin barrier function in addition to providing anti\u2010ultraviolet irradiation defense. The present study aimed to develop a new regimen that enhances skin barrier function by regulating skin pigmentation using low\u2010concentration imiquimod. Results showed that topical application of low\u2010concentration imiquimod effectively induced skin hyperpigmentation in the dorsal skin and external ear of mice without inducing inflammatory cell infiltration. An in vitro study also revealed that low\u2010concentration imiquimod did not induce any cytotoxic effects on melanoma cells but triggered excessive melanin synthesis. In coculture systems, low\u2010concentration imiquimod was noted to increase tyrosinase activity in a broader cellular context, revealing the potential role of neighboring cells in melanin production. The next\u2010generation sequencing result indicated that PKC\u03b7 and Dnm3 might regulate melanin synthesis and release during imiquimod treatment. Overall, our study presents new insights into the regulation of melanin production by low\u2010concentration imiquimod, both in a mice model and cultured cells. Furthermore, our study highlights the potential benefits of imiquimod in promoting melanin synthesis without causing skin disruptions or inducing inflammation, validating its potential to serve as a method for enhancing skin barrier functions by regulating the epidermal melanization reaction.<\/jats:p>","DOI":"10.1002\/tox.24332","type":"journal-article","created":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T02:50:21Z","timestamp":1716000621000},"page":"4360-4371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["RETRACTED: Low\u2010concentration imiquimod treatment promotes enhanced skin barrier functions through epidermal melanization reaction regulation"],"prefix":"10.1002","volume":"39","author":[{"given":"Tzu\u2010Kai","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Dermatology, Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation  Hualien Taiwan"},{"name":"School of 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