Analysis of the mechanism for the development of allergic skin inflammation and the application for its treatment:establishment of a modified allergic dermatitis model in mouse ear lobes by application of 12-O-tetradecanoyl phorbol 13-acetate: putative involvement of thymic stromal lymphopoietin and roles of histamine.
We established a novel allergic dermatitis model in mouse ear lobes in which antigen-nonspecific inflammation was induced by painting 12-O-tetradecanoylphorbol 13-acetate (TPA) between sensitization and challenge with picryl chloride (PiCl). This model has an advantage for analyzing atopic dermatitis-like inflammation within a short period. Analysis of the time course changes in the PiCl-induced swelling showed that the allergic inflammation was shifted from a delayed-type response to a biphasic response consisting of a weak immediate-phase response and a late-phase response by painting with TPA. The application of TPA increased the PiCl-induced infiltration of eosinophils and mast cells at the inflammatory site and shifted the cytokine milieu from Th1 to Th2. The expression of the Th2-inducing cytokine thymic stromal lymphopoietin (TSLP) mRNA was also increased by TPA. These findings suggested that the induction of antigen-nonspecific inflammation by TPA before the antigen challenge enhanced the Th2 response and modified the PiCl-induced delayed type-hypersensitivity. Using this model, we clarified that histamine plays significant roles in the early-phase swelling via H(1) receptors and the late-phase swelling via H(3)/H(4) receptors. Thus, we suggested the usefulness of the combined treatment with an H(1) antagonist and an H(4) antagonist for the suppression of atopic dermatitis.
Hirasawa
Noriyasu
N
Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan. hirasawa@mail.pharm.tohoku.ac.jp
Ohsawa
Yuhsuke
Y
Ishihara
Kenji
K
Seyama
Toshio
T
Hong
Jangja
J
Ohuchi
Kazuo
K
D000818:Animals; D016207:Cytokines / Q000502:physiology*; D003876:Dermatitis, Atopic / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology*; D004195:Disease Models, Animal; D004423:Ear; D006632:Histamine / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010853:Picryl Chloride / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D006632:Histamine; D013755:Tetradecanoylphorbol Acetate; D010853:Picryl Chloride; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse