Dermatophagoides farinae extract induces severe atopic dermatitis in NC/Nga mice, which is effectively suppressed by the administration of tacrolimus ointment.
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.
Oshio
Tomoyuki
T
Department of Biochemistry, Keio University Faculty of Pharmacy, Tokyo, Japan.
Sasaki
Yasuharu
Y
Funakoshi-Tago
Megumi
M
Aizu-Yokota
Eriko
E
Sonoda
Yoshiko
Y
Matsuoka
Hiroyuki
H
Kasahara
Tadashi
T
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*
D000485:Allergens; D018925:Chemokines; D007166:Immunosuppressive Agents; D009824:Ointments; D007073:Immunoglobulin E; D016559:Tacrolimus