Activation of aryl hydrocarbon receptor-nuclear factor erythroid 2-related factor 2 axis by epidermal growth factor receptor inhibitors: a possible mechanism for acneiform eruption

2016 Fiscal Year Final Research Report

• Project/Area Number: 15H06477
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Dermatology
• Research Institution: Kyushu University
• Principal Investigator: Tsuji Gaku 九州大学, 大学病院, 講師 (20423551)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Keywords: 芳香族炭化水素受容体

Outline of Final Research Achievements

Epidermal growth factor receptor inhibitors (EGFRIs) in the treatment for carcinomas cause acneiform eruption; however, its mechanism remains unknown. Because activation of aryl hydrocarbon receptor (AhR)-nuclear factor erythroid 2-related factor 2 (Nrf2) axis regulates keratinocyte differentiation and sebaceous gland activity, we hypothesized that activation of AhR-Nrf2 axis by EGFRIs might be involved in the development of acneiform eruption.
We administrated gefitinib (GEF) to normal human epidermal keratinocytes (NHEKs) and SEB-1 cells, a human sebocyte cell line. GEF induced up-regulation of CYP1A1 expression in NHEKs and SEB-1 cells, which was enhanced by 6-formylindolo (3,2-b) carbazole (FICZ), an AhR ligand. GEF induced up-regulation of Nrf2 in NHEKs and production of sebeum in SEB-1 cells, which was enhanced by FICZ. Collectively, acceleration of AhR-Nrf2 axis and sebeceous lipogenesis by EGFRIs may be important during acneiform eruption.

Free Research Field

皮膚科学