title: Kojic acid-induced IL-6 production in human keratinocytes plays a role in its anti-melanogenic activity in skin.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Bioscience Institute, AmorePacific Corporation R&D Center, Yongin, 446-729, Republic of Korea.
authors.forename: Hyunjung
authors.initials: H
authors.lastname: Choi
authors.forename: Kwangmi
authors.initials: K
authors.lastname: Kim
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Han
authors.forename: Hyun
authors.initials: H
authors.lastname: Choi
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Jin
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Shin
authors.forename: Tae Ryong
authors.initials: TR
authors.lastname: Lee
authors.forename: Ai-Young
authors.initials: AY
authors.lastname: Lee
authors.forename: Minsoo
authors.initials: M
authors.lastname: Noh
mesh_terms: D002450:Cell Communication; D002470:Cell Survival; D018920:Coculture Techniques; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008543:Melanins / Q000378:metabolism*; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010858:Pigmentation; D011753:Pyrones / Q000494:pharmacology*; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D008543:Melanins; D011753:Pyrones; C011890:kojic acid; D014442:Monophenol Monooxygenase