A novel atopic dermatitis model induced by topical application with dermatophagoides farinae extract in NC/Nga mice.
BACKGROUND
Atopic dermatitis is a chronically relapsing inflammatory skin disease. Animal models induced by relevant allergens play a very important role in the elucidation of the disease. The patients with atopic dermatitis are highly sensitized with mite allergens such as Dermatophagoides farinae (Df). Therefore, in the present study, we tried to develop a novel model for atopic dermatitis by repeated application with Df extract ointment.


METHODS
Df extract ointment was repeatedly applied to the back of NC/Nga mice together with barrier disruption. Atopic dermatitis-like skin lesions were evaluated by dermatitis scores, skin histology and immunological parameters. The effect of corticosteroid and calcineurin inhibitor was also examined.


RESULTS
Repeated application of Df extract ointment caused rapid increase in dermatitis scores. Clinical (skin dryness, erythema, edema and erosion) and histological symptoms (dermal and epidermal thickening, hyperkeratosis, parakeratosis and inflammatory cell infiltration) in this model were very similar to those in human atopic dermatitis. Serum total and Df-specific IgE levels were elevated in this model compared with normal mice, and draining lymph node cells isolated from the mice that exhibited dermatitis produced significant amounts of interleukin-5, interleukin-13 and interferon-gamma after re-stimulation with Df. Furthermore, current first-line drugs for the treatment of human atopic dermatitis, corticosteroid and tacrolimus ointments, were effective against the clinical and histological symptoms in this model.


CONCLUSIONS
These results suggest that the model we have established is useful for not only elucidating the pathogenesis of atopic dermatitis but also for evaluating therapeutic agents.
Yamamoto
Mina
M
Discovery Research Laboratory, Shionogi & Co., LTD., Osaka, Japan.
Haruna
Takayo
T
Yasui
Kiyoshi
K
Takahashi
Hisashi
H
Iduhara
Miho
M
Takaki
Shigeki
S
Deguchi
Masashi
M
Arimura
Akinori
A
D000305:Adrenal Cortex Hormones / Q000494:pharmacology / Q000627:therapeutic use; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001623:Betamethasone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D040001:Dermatophagoides farinae / Q000276:immunology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D015203:Reproducibility of Results; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use
D000305:Adrenal Cortex Hormones; D000485:Allergens; D007166:Immunosuppressive Agents; D018793:Interleukin-13; D015848:Interleukin-5; D007073:Immunoglobulin E; D007371:Interferon-gamma; C011175:betamethasone-17,21-dipropionate; D001623:Betamethasone; D016559:Tacrolimus