- •FICZ upregulated the expression of filaggrin in keratinocytes via AHR.
- •In dermatitis-affected mouse skin, the expression of filaggrin was recovered by FICZ.
- •FICZ improved mite-induced chronic dermatitis and TEWL in NC/Nga mice.
Chronic eczema such as atopic dermatitis imposes significant socio-econo-psychologic burdens on the affected individuals. In addition to conventional topical treatments, phototherapy is recommended for patients with extensive lesions. Although immunosuppression is believed to explain its primary effectiveness, the underlying mechanisms of phototherapy remain unsolved. Ultraviolet irradiation generates various tryptophan photoproducts including 6-formylindolo[3,2-b]-carbazole (FICZ). FICZ is known to be a potent endogenous agonist for aryl hydrocarbon receptor (AHR); however, the biological role of FICZ in chronic eczema is unknown.
To investigate the effect of FICZ on chronic eczema such as atopic dermatitis.
We stimulated HaCaT cells and normal human epidermal keratinocytes (NHEKs) with or without FICZ and then performed quantitative reverse transcriptase polymerase chain reaction, immunofluorescence, and siRNA treatment. We used the atopic dermatitis-like NC/Nga murine model and treated the mice for 2 weeks with either Vaseline® as a control, FICZ ointment, or betamethasone 17-valerate ointment. The dermatitis score, transepidermal water loss, histology, and expression of skin barrier genes and proteins were evaluated.
FICZ significantly upregulated the gene expression of filaggrin in both HaCaT cells and NHEKs in an AHR-dependent manner, but did not affect the gene expression of other barrier-related proteins. In addition, FICZ improved the atopic dermatitis-like skin inflammation, clinical scores, 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.
Abbreviations:FICZ (6-formylindolo[3,2-b]-carbazole), AHR (aryl hydrocarbon receptor), NHEKs (normal human epidermal keratinocytes), TEWL (transepidermal water loss), FLG (filaggrin), UV (ultraviolet)
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Published online: February 21, 2018
Accepted: February 19, 2018
Received in revised form: February 13, 2018
Received: July 6, 2017
© 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.