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Exp Dermatol ; 23(8): 568-72, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24903639

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.


Subject(s)
Dermatitis, Atopic/chemically induced , Dermatitis, Atopic/drug therapy , Dermatophagoides farinae , Disease Models, Animal , Immunosuppressive Agents/therapeutic use , Sirolimus/therapeutic use , Tissue Extracts/adverse effects , Administration, Topical , Animals , Cytokines/metabolism , Dermatitis, Atopic/metabolism , Female , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/pharmacology , Mice , Mice, Mutant Strains , Ointments , Phosphorylation , Signal Transduction/drug effects , Sirolimus/administration & dosage , Sirolimus/pharmacology , Skin/drug effects , Skin/metabolism , Skin/pathology , TOR Serine-Threonine Kinases/antagonists & inhibitors , TOR Serine-Threonine Kinases/drug effects , TOR Serine-Threonine Kinases/metabolism , Tissue Extracts/administration & dosage
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