title: Imiquimod induces apoptosis of human melanocytes.
abstract: Development of vitiligo-like hypopigmentary lesions associated with topical imiquimod has been reported. We hypothesized that mode of action of imiquimod in melanocytes may include triggering of apoptosis resulted in loss of cells, which may be a possible mechanism of imiquimod-induced hypopigmentary lesions. Therefore, we investigated whether imiquimod induces apoptosis of human melanocytes and also whether it modulates expression of apoptosis-related molecules in human melanocytes. Imiquimod treatment induced apoptosis of melanocytes, which was observed by TUNEL assay and Hoechst 33258 staining. Imiquimod-induced apoptosis was further shown by measuring mitochondrial membrane potential in melanocytes. The apoptotic activity of imiquimod was associated with caspase-3, Bcl-2 and mitogen-activated protein kinase expression in melanocytes. These results indicated that imiquimod induces apoptosis of melanocytes. These findings may provide a clue to understand pathogenesis of imiquimod-induced vitiligo-like hypopigmentary lesions.
authors.affiliation: Department of Otolaryngology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Joo Hee
authors.initials: JH
authors.lastname: Ahn
authors.forename: Sung Un
authors.initials: SU
authors.lastname: Kang
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Hwang
authors.forename: Mi Hye
authors.initials: MH
authors.lastname: Lee
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Pyun
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Kang
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects; D000634:Aminoquinolines / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D017496:Hypopigmentation; D000077271:Imiquimod; D020287:In Situ Nick-End Labeling; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014820:Vitiligo / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D019253:Proto-Oncogene Proteins c-bcl-2; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; D000077271:Imiquimod