Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 ointment (fingolimod) in NC/Nga mice
| Autor: | Satoshi Okuno, Sakura Sakurai, Takeyuki Kohno, Takumi Tsuji, Takuma Chikami, Rie Banno, Yuya Yoshida, Junya Hamazaki, Tetsuro Fujita, Ayano Kuroda |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
NC/Nga mice
0301 basic medicine Filaggrin Proteins Pharmacology Immunoglobulin E Ointments Mice 0302 clinical medicine Intermediate Filament Proteins hemic and lymphatic diseases Immunology and Allergy skin and connective tissue diseases Epidermal barrier function Dermatophagoides farinae integumentary system biology General Medicine Atopic dermatitis Mast cell Fingolimod medicine.anatomical_structure Betamethasone Female Filaggrin Immunosuppressive Agents medicine.drug lcsh:Immunologic diseases. Allergy medicine.medical_specialty Tacrolimus Dermatitis Atopic 03 medical and health sciences medicine Animals Immunologic Factors Transepidermal water loss Fingolimod Hydrochloride business.industry medicine.disease FTY720 ointment Dermatology eye diseases body regions Disease Models Animal 030104 developmental biology 030228 respiratory system biology.protein lcsh:RC581-607 business |
| Zdroj: | Allergology International, Vol 65, Iss 2, Pp 172-179 (2016) |
| ISSN: | 1323-8930 |
| DOI: | 10.1016/j.alit.2015.10.009 |
| Popis: | Background The increasing incidence and prevalence of atopic dermatitis (AD) demands new therapeutic 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 (betamethasone 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, histochemical 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. |
| Databáze: | OpenAIRE |
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