title: Topically applied semaphorin 3A ointment inhibits scratching behavior and improves skin inflammation in NC/Nga mice with atopic dermatitis.
abstract: BACKGROUND
  Epidermal hyperinnervation in atopic dermatitis (AD) is activated directly by various external stimuli, causing enhanced itching. Nerve density is regulated by the nerve repulsion factor semaphorin 3A (Sema3A), along with nerve elongation factors.
  
  
  OBJECTIVE
  To investigate the effects of Sema3A ointment in the NC/Nga mouse model of AD.
  
  
  METHODS
  An AD-like phenotype was induced by repeated application of Dermatophagoides farinae body (Dfb) ointment to the dorsal skin of NC/Nga mice. Vaseline, heparinoid, betamethasone, tacrolimus and recombinant Sema3A ointments were applied to the lesional skin once a day for 4 days. Transepidermal water loss (TEWL) was measured before and after each treatment. We also scored the degree of dermatitis and recorded videos to observe scratching behavior. Subsequently, we collected skin samples from these mice for histological analyses.
  
  
  RESULTS
  Topical application of Sema3A, betamethasone and tacrolimus ointments significantly inhibited scratching behavior and improved dermatitis scores in Dfb-treated mice compared with control mice, whereas vaseline and heparinoid had no effects. A significant improvement of TEWL was observed only in Sema3A ointment-treated mice. Moreover, Sema3A ointment reduced the densities of PGP9.5- and substance P-immunoreactive nerve fibers in the epidermis and the numbers of inflammatory cells, such as CD4 immunoreactive T cells and eosinophils, and improved acanthosis in the Dfb-treated mice compared with controls.
  
  
  CONCLUSIONS
  Sem3A ointment may have therapeutic efficacy in patients with pruritus and dermatitis of AD.
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Negi
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Tominaga
authors.forename: Suhandy
authors.initials: S
authors.lastname: Tengara
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kamo
authors.forename: Kenichi
authors.initials: K
authors.lastname: Taneda
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Suga
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Takamori
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001623:Betamethasone / Q000494:pharmacology; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D040001:Dermatophagoides farinae / Q000276:immunology*; D004359:Drug Therapy, Combination; D004817:Epidermis / Q000187:drug effects / Q000294:innervation / Q000382:microbiology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009411:Nerve Endings / Q000187:drug effects; D009824:Ointments / Q000494:pharmacology*; D011537:Pruritus / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D040121:Semaphorin-3A / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D009824:Ointments; D040121:Semaphorin-3A; D001623:Betamethasone; D016559:Tacrolimus