Mari Kiyomatsu-Oda1, Hiroshi Uchi2, Saori Morino-Koga3, Masutaka Furue4. 1. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: mari1019@med.kyushu-u.ac.jp. 2. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. 3. Department of Cell Division, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan. 4. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Abstract
BACKGROUND: 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. OBJECTIVE: To investigate the effect of FICZ on chronic eczema such as atopic dermatitis. METHODS: 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. RESULTS: 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. CONCLUSION: These findings highlight the beneficial role of FICZ-AHR and provide a new strategic basis for developing new drugs for chronic eczema.
BACKGROUND: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. OBJECTIVE: To investigate the effect of FICZ on chronic eczema such as atopic dermatitis. METHODS: 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. RESULTS: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. CONCLUSION: These findings highlight the beneficial role of FICZ-AHR and provide a new strategic basis for developing new drugs for chronic eczema.
Authors: Rebecca Justiniano; Lohanna de Faria Lopes; Jessica Perer; Anh Hua; Sophia L Park; Jana Jandova; Maurício S Baptista; Georg T Wondrak Journal: Photochem Photobiol Date: 2020-09-14 Impact factor: 3.421
Authors: Laura Lozza; Pedro Moura-Alves; Teresa Domaszewska; Carolina Lage Crespo; Ioana Streata; Annika Kreuchwig; Andreas Puyskens; Marina Bechtle; Marion Klemm; Ulrike Zedler; Bogdan Silviu Ungureanu; Ute Guhlich-Bornhof; Anne-Britta Koehler; Manuela Stäber; Hans-Joachim Mollenkopf; Robert Hurwitz; Jens Furkert; Gerd Krause; January Weiner; António Jacinto; Ioana Mihai; Maria Leite-de-Moraes; Frank Siebenhaar; Marcus Maurer; Stefan H E Kaufmann Journal: Sci Rep Date: 2019-07-26 Impact factor: 4.379
Authors: Elisa Roztocil; Christine L Hammond; Mithra O Gonzalez; Steven E Feldon; Collynn F Woeller Journal: Sci Rep Date: 2020-05-21 Impact factor: 4.379