Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 ointment (fingolimod) in NC/Nga mice
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: Fe...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-04-01
|
| Series: | Allergology International |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1323893015002051 |
| _version_ | 1818572400515612672 |
|---|---|
| author | Takumi Tsuji Satoshi Okuno Ayano Kuroda Junya Hamazaki Takuma Chikami Sakura Sakurai Yuya Yoshida Rie Banno Tetsuro Fujita Takeyuki Kohno |
| author_facet | Takumi Tsuji Satoshi Okuno Ayano Kuroda Junya Hamazaki Takuma Chikami Sakura Sakurai Yuya Yoshida Rie Banno Tetsuro Fujita Takeyuki Kohno |
| author_sort | Takumi Tsuji |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T18:56:34Z |
| format | Article |
| id | doaj.art-60efde4c8e854c1d9a1a8006d5451d69 |
| institution | Directory Open Access Journal |
| issn | 1323-8930 |
| language | English |
| last_indexed | 2024-12-14T18:56:34Z |
| publishDate | 2016-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Allergology International |
| spelling | doaj.art-60efde4c8e854c1d9a1a8006d5451d692022-12-21T22:51:05ZengElsevierAllergology International1323-89302016-04-0165217217910.1016/j.alit.2015.10.009Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 ointment (fingolimod) in NC/Nga miceTakumi Tsuji0Satoshi Okuno1Ayano Kuroda2Junya Hamazaki3Takuma Chikami4Sakura Sakurai5Yuya Yoshida6Rie Banno7Tetsuro Fujita8Takeyuki Kohno9Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, JapanDepartment of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, JapanDepartment of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, JapanDepartment of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, JapanDepartment of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, JapanDepartment of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, JapanDepartment of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, JapanDepartment of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, JapanResearch Institute for Production and Development, Kyoto, JapanDepartment of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, JapanBackground: 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.http://www.sciencedirect.com/science/article/pii/S1323893015002051Atopic dermatitisEpidermal barrier functionFilaggrinFTY720 ointmentNC/Nga mice |
| spellingShingle | Takumi Tsuji Satoshi Okuno Ayano Kuroda Junya Hamazaki Takuma Chikami Sakura Sakurai Yuya Yoshida Rie Banno Tetsuro Fujita Takeyuki Kohno Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 ointment (fingolimod) in NC/Nga mice Allergology International Atopic dermatitis Epidermal barrier function Filaggrin FTY720 ointment NC/Nga mice |
| title | Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 ointment (fingolimod) in NC/Nga mice |
| title_full | Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 ointment (fingolimod) in NC/Nga mice |
| title_fullStr | Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 ointment (fingolimod) in NC/Nga mice |
| title_full_unstemmed | Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 ointment (fingolimod) in NC/Nga mice |
| title_short | Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 ointment (fingolimod) in NC/Nga mice |
| title_sort | therapeutic approach to mite induced intractable dermatitis using novel immunomodulator fty720 ointment fingolimod in nc nga mice |
| topic | Atopic dermatitis Epidermal barrier function Filaggrin FTY720 ointment NC/Nga mice |
| url | http://www.sciencedirect.com/science/article/pii/S1323893015002051 |
| work_keys_str_mv | AT takumitsuji therapeuticapproachtomiteinducedintractabledermatitisusingnovelimmunomodulatorfty720ointmentfingolimodinncngamice AT satoshiokuno therapeuticapproachtomiteinducedintractabledermatitisusingnovelimmunomodulatorfty720ointmentfingolimodinncngamice AT ayanokuroda therapeuticapproachtomiteinducedintractabledermatitisusingnovelimmunomodulatorfty720ointmentfingolimodinncngamice AT junyahamazaki therapeuticapproachtomiteinducedintractabledermatitisusingnovelimmunomodulatorfty720ointmentfingolimodinncngamice AT takumachikami therapeuticapproachtomiteinducedintractabledermatitisusingnovelimmunomodulatorfty720ointmentfingolimodinncngamice AT sakurasakurai therapeuticapproachtomiteinducedintractabledermatitisusingnovelimmunomodulatorfty720ointmentfingolimodinncngamice AT yuyayoshida therapeuticapproachtomiteinducedintractabledermatitisusingnovelimmunomodulatorfty720ointmentfingolimodinncngamice AT riebanno therapeuticapproachtomiteinducedintractabledermatitisusingnovelimmunomodulatorfty720ointmentfingolimodinncngamice AT tetsurofujita therapeuticapproachtomiteinducedintractabledermatitisusingnovelimmunomodulatorfty720ointmentfingolimodinncngamice AT takeyukikohno therapeuticapproachtomiteinducedintractabledermatitisusingnovelimmunomodulatorfty720ointmentfingolimodinncngamice |