Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 ointment (fingolimod) in NC/Nga mice
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- Tsuji Takumi
- Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
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- Okuno Satoshi
- Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
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- Kuroda Ayano
- Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
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- Hamazaki Junya
- Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
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- Chikami Takuma
- Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
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- Sakurai Sakura
- Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
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- Yoshida Yuya
- Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
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- Banno Rie
- Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
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- Fujita Tetsuro
- Research Institute for Production and Development
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- Kohno Takeyuki
- Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University Research Institute for Production and Development
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説明
Background: The increasing incidence and prevalence of atopic dermatitis (AD) demands new thera- peutic approaches for treating the disease. We investigated the therapeutic efficacy of immunomodulator FTY720 ointment (fingolimod) for mite-induced intractable AD using an NC/Nga mouse model. Methods: Female NC/Nga mice that developed severe AD were divided into four groups: (1) FTY720 (0.001% FTY720 ointment), (2) tacrolimus (tacrolimus hydrate ointment) (3) betamethasone (betame- thasone ointment), and (4) ointment base (hydrophilic petrolatum), all of which received treatment six times per week. Therapeutic efficacy after two weeks was evaluated in terms of AD severity, histo- chemical observations (epidermal hypertrophy, mast cell accumulation, and CD3+ T cell infiltration), transepidermal water loss (TEWL), and epidermal barrier function (filaggrin expression). Results: Betamethasone treatment showed little effect, confirming that the AD was intractable. In the FTY720 group, AD improved significantly compared with the ointment base group, as did epidermal hypertrophy, mast cell accumulation, and CD3+ T cell infiltration. In contrast, AD in the tacrolimus and betamethasone groups did not improve significantly, nor did epidermal hypertrophy or mast cell accumulation. Furthermore, in the FTY720 group, TEWL decreased significantly compared with the ointment base group, and filaggrin expression significantly increased compared with the betamethasone and ointment base groups. Conclusions: FTY720 ointment is a promising candidate for treatment of intractable AD. These findings also provide the first evidence that FTY720 ointment ameliorates epidermal barrier function.
収録刊行物
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- Allergology International
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Allergology International 65 (2), 172-179, 2016
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