title: Dermatophagoides farinae extract induces severe atopic dermatitis in NC/Nga mice, which is effectively suppressed by the administration of tacrolimus ointment.
abstract: Atopic dermatitis (AD) is a chronic inflammatory skin disease, which is accompanied by marked increases in the levels of inflammatory cells, including mast cells and eosinophils as well as T cells and macrophages. To investigate the expression pattern of chemokines in AD, a house dust mite, Dermatophagoides farinae extracts (DfE)-induced NC/Nga AD model was developed in mice, and this model was used to determine the expression levels of chemokines in atopic lesions using DNA microarrays and RT-PCR. When NC/Nga mice were repeatedly treated with DfE for 4 to 7 weeks on the back skin, the mRNA expression levels of CCL20/LARC, CCL24/eotaxin-2, CCL17/TARC, and CCL11/eotaxin-1 were markedly induced and lesser of CCL2/MCP-1, within the inflammatory lesion of the back skin. Immunohistochemical staining revealed the expression of these chemokines in the epidermis and dermis of DfE-treated NC/Nga mice. Interestingly, repeated application of tacrolimus ointment potently inhibited DfE-induced atopic dermatitis in NC/Nga mice concomitant with the inhibition of these changes in chemokine gene and protein expression levels particularly of CCL20/LARC, CCL17/TARC, and CCL11/eotaxin-1. These data indicate that severe atopic dermatitis induced by DfE accompanies elevated chemokine levels, and it was proposed that tacrolimus ointment is beneficial for the treatment of severe AD.
authors.affiliation: Department of Biochemistry, Keio University Faculty of Pharmacy, Tokyo, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Oshio
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Megumi
authors.initials: M
authors.lastname: Funakoshi-Tago
authors.forename: Eriko
authors.initials: E
authors.lastname: Aizu-Yokota
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Sonoda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsuoka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kasahara
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D018925:Chemokines / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D040001:Dermatophagoides farinae / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D051379:Mice; D009824:Ointments; D016559:Tacrolimus / Q000008:administration & dosage*
chemical_list: D000485:Allergens; D018925:Chemokines; D007166:Immunosuppressive Agents; D009824:Ointments; D007073:Immunoglobulin E; D016559:Tacrolimus