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Immunosuppressive effects of fisetin against dinitrofluorobenzene-induced atopic dermatitis-like symptoms in NC/Nga mice
Affiliation:1. Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Canada;2. Department of Immunology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Canada;3. Oral Ecology Research Group, Faculty of Dentistry, Laval University, Quebec, QC, Canada;1. Department of Pharmaceutical Analysis, College of Pharmacy, Third Military Medical University, Chongqing, China;2. Base for Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, China;1. Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea;2. Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea;3. Department of Food Science & Technology, Hoseo University, 20, Hoseo-ro 79 beon-gil, Baebang-eup, Asan, Chungcheongnam-do 31499, Republic of Korea;1. Institutes of Entrepreneurial BioConvergence, Seoul National University, Seoul 151-742, Republic of Korea;2. Laboratory of Virology, School of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea;3. Korea Food Research Institute, 1201-62, Anyangpangyo-ro, Bundang-gu, Seognam-si, Kyeonggi-do 463-746, Republic of Korea;4. University of Science and Technology (UST), Daejeon 305-350, Republic of Korea;5. School of Life Sciences, Gwangju Institute of Science and Technology (GIST), 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712, Republic of Korea;6. Academy of Immunology and Microbiology (AIM), Institute for Basic Science (IBS), Pohang, Republic of Korea;7. Division of Integrative Biosciences and Biotechnology (IBB), Pohang University of Science and Technology, Pohang, Republic of Korea;8. ViroMed Co., Ltd., Seoul 151-747, Korea
Abstract:Atopic dermatitis (AD) is a multifactorial chronic skin disorder that is increasing in prevalence globally. In NC/Nga mice, repetitive epicutaneous applications of 2-4-dinitrofluorobenzene (DNFB) induces AD-like clinical symptoms. Bioflanonol fisetin (3,7,3′,4′-tetrahydroxyflavone) is a dietary component found in plants, fruits and vegetables. Fisetin has various physiological effects that include anti-oxidation, anti-angiogenesis, anti-carcinogenesis and anti-inflammation. In this study, we investigated whether fisetin relieves AD-like clinical symptoms induced by repeated DNFB treatment in NC/Nga mice. Fisetin significantly inhibited infiltration of inflammatory cells including eosinophils, mast cells and CD4+ T and CD8+ T cells, and suppressed the expressions of cytokines and chemokines associated with dermal infiltrates in AD-like skin lesions. Total serum immunoglobulin E (IgE) levels and the ratio of phospho-NF-κB p65 to total NF-κB p65 were markedly reduced by fisetin. Fisetin also reduced the production of interferon-gamma and interleukin-4 by activated CD4+ T cells in a dose-dependent manner, whereas the anti-inflammatory cytokine, interleukin-10 was increased. These results implicate fisetin as a potential therapeutic for AD.
Keywords:Atopic dermatitis  Fisetin  2-4-Dinitrofluorobenzene  NC/Nga  NF-κB
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