{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T13:04:16Z","timestamp":1779109456240,"version":"3.51.4"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T00:00:00Z","timestamp":1633478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY16H110001"],"award-info":[{"award-number":["LY16H110001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Imiquimod plays an important role in the management of condyloma and premalignant lesions. Successively, an increase of hypopigmented lesions following imiquimod application has been reported. However, the mechanisms of imiquimod on melanocytes remain unclear. This study was designed to assess the effect of Imiquimod on the functions of melanocytes in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Primary cultured melanocytes were isolated from normal control skin tissue. After incubation with imiquimod for 48\u2009h in vitro, cell viability was analyzed by cell counting kit\u20108 assay. Apoptosis was detected using the Annexin V\u2010fluorescein\u20105\u2010isothiocyanate flow cytometry assay. Melanin content and tyrosinase activity in melanocytes were measured by colorimetric method and the modified dopachrome method. The production of inflammatory cytokine interleukin 8 (IL\u20108), IL\u20106, and soluble ICAM\u20101 (soluble Intercellular Adhesion Molecule\u20101[sICAM\u20101]) in melanocytes were measured by enzyme\u2010linked immunosorbent assay (ELISA). Toll\u2010like receptor 7 (TLR7), toll\u2010like receptor 9 (TLR9) protein, and autophagy\u2010related proteins microtubule\u2010associated protein 1A\/1B\u2010light chain 3 (LC3\u2010II), p62, mechanistic target of rapamycin (mTOR), and Atg5 were assessed using western blot analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Imiquimod significantly inhibited the activity of tyrosinase activity and decreased melanin content in melanocytes and significantly increased apoptosis and IL\u20106, IL\u20108, and sICAM\u20101 production in melanocytes. Moreover, the expression of TLR7 and TLR9 proteins were significantly increased, and the expression of mTOR, p62 protein were markedly decreased, but the expression of LC3II\/I and Atg5 protein were significantly increased in melanocytes after incubating with imiquimod.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study shows that imiquimod directly inhibits melanogenesis and increases melanocyte apoptosis rates. These effects combined with the upregulation of TLR7 and TLR9 together with increased autophagy activity and inflammatory cytokines production, might be the main reasons leading to hypopigmented lesions after imiquimod application.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.543","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T23:30:51Z","timestamp":1633735851000},"page":"70-77","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Imiquimod induced vitiligo\u2010like lesions\u2014A consequence of modified melanocyte function"],"prefix":"10.1002","volume":"10","author":[{"given":"Haiyan","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Dermatology, Sir Run Run Shaw Hospital Zhejiang University Medical College Hangzhou Zhejiang 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