An improved mouse model of atopic dermatitis and suppression of skin lesions by an inhibitor of Tec family kinases.
BACKGROUND
Atopic dermatitis is a chronic or chronically relapsing, pruritic inflammatory skin disease. The incidence of atopic dermatitis has dramatically increased during the past three decades in industrialized countries. We attempted to develop an improved method to induce an animal model of atopic dermatitis and to use it to evaluate the efficacy of a Tec family kinase inhibitor.


METHODS
We treated dermatitis-prone inbred mice, NC/Nga, by repetitive epicutaneous applications of a house dust mite allergen and staphylococcal enterotoxin B to induce atopic dermatitis-like skin lesions.


RESULTS
We established a highly efficient protocol to induce skin lesions in NC/Nga mice, which were histologically and immunologically similar to human atopic dermatitis. Similar to human patients, serum IgE levels were increased in dermatitis-induced mice. Consistent with the proposed roles of infiltrated immune cells in the pathogenesis of human atopic dermatitis, skin lesions were treatable with terreic acid, an inhibitor of Tec family kinases, as well as dexamethasone.


CONCLUSIONS
We established a highly efficient, highly reproducible protocol to induce skin lesions in NC/Nga mice and successfully applied it to show the efficacy of terreic acid in treating skin lesions. This mouse model of atopic dermatitis will be useful to study the pathogenetic processes of atopic dermatitis and to evaluate the efficacy of drug candidates.
Kawakami
Yuko
Y
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. yuko@liai.org
Yumoto
Kenji
K
Kawakami
Toshiaki
T
D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage; D003876:Dermatitis, Atopic / Q000201:enzymology / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000008:administration & dosage / Q000627:therapeutic use
D039741:Antigens, Dermatophagoides; D004768:Enterotoxins; D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; D011809:Quinones; C031818:enterotoxin B, staphylococcal; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; C009400:terreic acid