Abstract | BACKGROUND:
Kojic acid is a fungal metabolite widely used in medicinal and cosmetic formulations as a skin-lightening agent based on its de-pigmenting activity. Although in human clinical studies kojic acid has been shown to be effective in the treatment of hyper- pigmentation disorders such as melasma, the reasons for its apparent lack of anti-melanogenic activity in cultured mammalian melanocytes are unclear. OBJECTIVES: This study was aimed to elucidate pharmacological mechanisms of the in vivo anti-melanogenic activity of kojic acid in human skin. METHODS: A primary human melanocyte and keratinocyte co-culture system was used to evaluate whether kojic-acid-induced changes in keratinocytes were associated with anti-melanogenic activities in melanocytes. The cytokine secretion profiles in response to kojic acid were analyzed. RESULTS:
Kojic acid increased interleukin (IL)-6 and IL-8 production in melanocyte/keratinocyte co-cultures; however, IL-6 directly inhibited melanogenesis whereas IL-8 did not. In melanocyte monocultures, kojic acid did not increase IL-6 production whereas in keratinocyte monocultures it significantly up-regulated IL-6 gene and protein expression. Therefore, the up-regulation of IL-6 in melanocyte/keratinocyte co-cultures seems to be originated from kojic acid-induced changes in keratinocytes. Anti-IL-6 antibody treatment antagonized the anti-melanogenic effect of kojic acid on the co-cultures. CONCLUSIONS: The pharmacological mechanism of kojic acid to explain clinically effective anti-melanogenic activity on hyper-pigmented skin is associated with the kojic acid-induced IL-6 production in keratinocytes. The cross-talk between melanocytes and keratinocytes should be determined in future studies on the pharmacological mechanisms of clinically effective dermatological drugs acting on the epidermis.
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Authors | Hyunjung Choi, Kwangmi Kim, Jiyeon Han, Hyun Choi, Sun Hee Jin, Eun Kyung Lee, Dong Wook Shin, Tae Ryong Lee, Ai-Young Lee, Minsoo Noh |
Journal | Journal of dermatological science
(J Dermatol Sci)
Vol. 66
Issue 3
Pg. 207-15
(Jun 2012)
ISSN: 1873-569X [Electronic] Netherlands |
PMID | 22464230
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Interleukin-6
- Interleukin-8
- Melanins
- Pyrones
- kojic acid
- Monophenol Monooxygenase
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Topics |
- Cell Communication
- Cell Survival
- Coculture Techniques
- Humans
- Interleukin-6
(metabolism)
- Interleukin-8
(metabolism)
- Keratinocytes
(cytology, drug effects, metabolism)
- Melanins
(metabolism)
- Melanocytes
(cytology, drug effects, metabolism)
- Monophenol Monooxygenase
(metabolism)
- Pigmentation
- Pyrones
(pharmacology)
- Skin
(cytology, drug effects, metabolism)
- Up-Regulation
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