Study on the molecular mechanism whereby cosmetic skin-whitening ingredients induce leukoderma

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22885
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Tokyo Medical University
• Principal Investigator: Katahira Yasuhiro 東京医科大学, 医学部, 助教(特任) (80881458)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 白斑症 / 感作 / ロドデノール / h-CLAT / h-CLATw/M / メラノサイト / 樹状細胞 / 共培養

Outline of Final Research Achievements

In 2013, the active ingredient of whitening cosmetics, rhododenol (RD), was regarded as a causative agent of vitiligo, but an in vitro experiment to detect its toxicity has not yet been established, and the mechanism of vitiligo is also not elusive.
We hypothesized that cell death of melanocytes, which are highly sensitive to RD, is caused by activating dendritic cells in the subskin layer and inducing autoimmunity, and established a new experimental system in which a melanoma cell layer was added to h-CLAT. This made it possible to evaluate the immunotoxicity of RD in the form of increased expression of the CD86 molecule, which is an index of sensitization, from the THP-1 cells in the lower layer. We also found that reactive oxygen species and extracellular ATP are involved in the activation of dendritic cells using this system.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究で開発したin vitro実験系によって、事前の安全性試験でその毒性を知る事ができなかった化粧品成分のリスクを評価できた。ヒトの皮下の反応を模したこの実験系を用いる事で、ロドデノールによる白斑症発症までの詳細なメカニズムを解明できることが期待される。
また、h-CLATに追加する細胞層を別種の細胞に変えることで、特定の体組織の細胞との反応を介して間接的に免疫細胞を感作するような薬物毒性のスクリーニングも可能となる。
本成果は、これまで検知できなかった薬品の毒性評価を可能にした事で、化粧品、製薬業界において有用な新規成分の研究開発を促す事が期待されるものである。