title: Topical application of rapamycin ointment ameliorates Dermatophagoides farina body extract-induced atopic dermatitis in NC/Nga mice.
abstract: Atopic dermatitis (AD), a chronic inflammatory skin disease characterized by relapsing eczema and intense prurigo, requires effective and safe pharmacological therapy. Recently, rapamycin, an mTOR (mammalian target of rapamycin) inhibitor, has been reported to play a critical role in immune responses and has emerged as an effective immunosuppressive drug. In this study, we assessed whether inhibition of mTOR signalling could suppress dermatitis in mice. Rapamycin was topically applied to inflamed skin in a murine AD model that was developed by repeated topical application of Dermatophagoides farina body (Dfb) extract antigen twice weekly for 7 weeks in NC/Nga mice. The efficacy of topical rapamycin treatment was evaluated immunologically and serologically. Topical application of rapamycin reduced inflammatory cell infiltration in the dermis, alleviated the increase of serum IgE levels and resulted in a significant reduction in clinical skin condition score and marked improvement of histological findings. In addition, increased mTOR phosphorylation in the lesional skin was observed in our murine AD model. Topical application of rapamycin ointment inhibited Dfb antigen-induced dermatitis in NC/Nga mice, promising a new therapy for atopic dermatitis.
authors.affiliation: Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.forename: Mari
authors.initials: M
authors.lastname: Tanaka
authors.forename: Mari
authors.initials: M
authors.lastname: Wataya-Kaneda
authors.forename: Lingli
authors.initials: L
authors.lastname: Yang
authors.forename: Ayumi
authors.initials: A
authors.lastname: Nakamura
authors.forename: Shoji
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Mostafa
authors.initials: M
authors.lastname: Attia
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Murota
authors.forename: Ichiro
authors.initials: I
authors.lastname: Katayama
mesh_terms: D000287:Administration, Topical; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D040001:Dermatophagoides farinae; D004195:Disease Models, Animal; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008817:Mice, Mutant Strains; D009824:Ointments; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D014020:Tissue Extracts / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D009824:Ointments; D014020:Tissue Extracts; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: atopic dermatitis; mTOR; rapamycin