title: Differences in therapeutic effects of topically applied corticosteroid and tacrolimus on atopic dermatitis-like symptoms in NC/Nga mice.
abstract: BACKGROUND
  Topical corticosteroid and calcineurin inhibitor have similar therapeutic benefits in atopic dermatitis (AD), but the differences in therapeutic mechanisms of action of these agents against AD symptoms are not fully understood.
  
  
  OBJECTIVE
  This study was performed to examine the different effects of topical betamethasone valerate (BMV), clobetasol propionate (CBP), and tacrolimus (TAC) on itch-related behavior and dermatitis in NC/Nga mice with AD-like symptoms.
  
  
  METHODS
  AD-like dermatitis was induced in the dorsal skin of NC/Nga mice by repeated topical application of Dermatophagoides farinae body (Dfb) ointment twice weekly for three weeks. Mice with dermatitis scores over 5 were divided into five groups with equal dermatitis scores and treated with BMV, CBP, TAC, or Vaseline (Vas) once daily for two consecutive days, or were not treated (NT). Scratching behavior was analyzed using a SCLABA®-Real system. Transepidermal water loss (TEWL) before and after treatment was measured using a Tewameter®TM210. Skin collected from each group was analyzed histologically.
  
  
  RESULTS
  After the second treatment, dermatitis showed significantly greater improvement in the CBP and TAC-treated groups than in the Vas-treated and NT groups. The numbers of scratching bouts were significantly lower in CBP and TAC-treated mice than in Vas-treated mice. TEWL was significantly lower in TAC-, but not in CBP-, treated mice than in Vas-treated mice. Immunohistochemical examination showed that BMV, CBP and TAC did not reduce the increased densities of epidermal protein gene product 9.5- and substance P-immunoreactive fibers. The numbers of dermal CD4-immunoreactive T cells were significantly lower in BMV and CBP-treated mice than in Vas-treated and NT mice. The numbers of dermal eosinophils were significantly lower in BMV, CBP and TAC-treated mice than in Vas-treated and NT mice, with CBP showing the strongest effect. CBP significantly reduced epidermal thickness compared with Vas and NT. There were no significant differences in the numbers of interleukin-31-immunoreactive cells and mast cells, or in expression of epidermal thymic stromal lymphopoietin among all five groups.
  
  
  CONCLUSIONS
  The therapeutic potency of TAC against AD-like symptoms, including pruritus, is equal to that of the corticosteroid CBP. Epidermal innervation of sensory nerves itself might not be related to the therapeutic effects of topical tacrolimus and corticosteroids in its early phase.
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan; Department of Dermatology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Noguchi
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Tominaga
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Matsuda
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Kamata
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Umehara
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Kyi Chan
authors.initials: KC
authors.lastname: Ko
authors.affiliation: Department of Dermatology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Suga
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan; Department of Dermatology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan. Electronic address: ktakamor@juntendo.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takamori
mesh_terms: D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001624:Betamethasone Valerate / Q000008:administration & dosage / Q000627:therapeutic use; D002990:Clobetasol / Q000008:administration & dosage / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000209:etiology; D040001:Dermatophagoides farinae / Q000276:immunology; D004195:Disease Models, Animal; D004643:Emollients / Q000008:administration & dosage / Q000627:therapeutic use; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D009824:Ointments / Q000008:administration & dosage / Q000627:therapeutic use; D010577:Petrolatum / Q000008:administration & dosage / Q000627:therapeutic use; D011537:Pruritus / Q000188:drug therapy*; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000305:Adrenal Cortex Hormones; D016207:Cytokines; D004643:Emollients; D007166:Immunosuppressive Agents; D009824:Ointments; D010577:Petrolatum; D001624:Betamethasone Valerate; D002990:Clobetasol; D043222:Ubiquitin Thiolesterase; C496976:Uchl1 protein, mouse; D016559:Tacrolimus; D000094632:Thymic Stromal Lymphopoietin
keywords: Atopic dermatitis; Corticosteroid; Epidermal nerve fiber; Pruritus; Tacrolimus