title: Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 ointment (fingolimod) in NC/Nga mice.
abstract: 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.
authors.affiliation: Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okuno
authors.affiliation: Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Kuroda
authors.affiliation: Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Hamazaki
authors.affiliation: Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Chikami
authors.affiliation: Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
authors.forename: Sakura
authors.initials: S
authors.lastname: Sakurai
authors.affiliation: Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Banno
authors.affiliation: Research Institute for Production and Development, Kyoto, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan; Research Institute for Production and Development, Kyoto, Japan. Electronic address: kohno@pharm.setsunan.ac.jp.
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Kohno
mesh_terms: D000818:Animals; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D040001:Dermatophagoides farinae / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D000091344:Filaggrin Proteins; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000276:immunology; D007155:Immunologic Factors / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007381:Intermediate Filament Proteins / Q000378:metabolism; D051379:Mice; D009824:Ointments; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D000091344:Filaggrin Proteins; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D007381:Intermediate Filament Proteins; D009824:Ointments; D007073:Immunoglobulin E; D000068876:Fingolimod Hydrochloride; D016559:Tacrolimus
keywords: Atopic dermatitis; Epidermal barrier function; FTY720 ointment; Filaggrin; NC/Nga mice