FICZ improves atopic dermatitis by enhancement of fillagrin production.

• Project/Area Number: 15K09770
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kyushu University
• Principal Investigator: Uchi Hiroshi 九州大学, 医学研究院, 准教授 (50437787)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: アトピー性皮膚炎 / FICZ / アリル炭化水素受容体 / フィラグリン / 表皮バリア / 経表皮水分蒸散量

Outline of Final Research Achievements

Atopic dermatitis imposes significant socio-econo-psychologic burdens on the affected individuals and phototherapy is recommended for patients with extensive lesions. Ultraviolet irradiation generates various tryptophan photoproducts including 6-formylindolo[3,2-b]-carbazole (FICZ). FICZ is a potent endogenous agonist for aryl hydrocarbon receptor (AHR). We found FICZ significantly upregulated the gene expression of filaggrin in cultured keratinicytes in an AHR-dependent manner. In addition, FICZ improved the atopic dermatitis-like skin inflammation and transepidermal water loss in NC/Nga mice compared with those of control mice. On histology, FICZ significantly reduced the epidermal and dermal thickness as well as the number of mast cells. Topical FICZ also significantly reduced the gene expression of Il22. These findings highlight the beneficial role of FICZ-AHR and provide a new strategic basis for developing new drugs for chronic eczema.

Research Products

• [Journal Article] Protective role of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous ligand for arylhydrocarbon receptor, in chronic mite-induced dermatitis. (2018)
  • Author(s): Kiyomatsu-Oda M, Uchi H, Morino-Koga S, Furue M.
  • Journal Title: Journal of Dermatological Science Volume: in press
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Aryl hydrocarbon receptor activation restores filaggrin expression via OVOL1 in atopic dermatitis. (2017)
  • Author(s): Tsuji G, Hashimoto-Hachiya A, Kiyomatsu-Oda M, Takemura M, Ohno F, Ito T, Morino-Koga S, Mitoma C, Nakahara T, Uchi H, Furue M.
  • Journal Title: Cell Death & Disease Volume: 8
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Tryptophan photoproduct 6-formylindolo[3,2-b]carbazole, FICZ, inhibits atopic dermatitis - A clue linking “photo-effectiveness” to aryl hydrocarbon receptor- (2017)
  • Author(s): Mari Kiyomatsu-Oda, Hiroshi Uchi, Saori Morino-Koga, Masutaka Furue
  • Organizer: Society for Investigative Dermatology 2017 Annual Meeting
  • Int'l Joint Research
• [Presentation] The tryptophan photoproduct FICZ improves atopic dermatitis by enhancement of fillagrin production (2017)
  • Author(s): Hiroshi Uchi, Mari Kiyomatsu-Oda, Masutaka Furue
  • Organizer: the 47th Annual ESDR Meeting 2017
  • Int'l Joint Research