TY - JOUR
T1 - Analysis of the mechanism for the development of allergic skin inflammation and the application for its treatment
T2 - 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
AU - Hirasawa, Noriyasu
AU - Ohsawa, Yuhsuke
AU - Ishihara, Kenji
AU - Seyama, Toshio
AU - Hong, Jang Ja
AU - Ohuchi, Kazuo
PY - 2009
Y1 - 2009
N2 - 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 immediatephase 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 H1 receptors and the late-phase swelling via H3/H4 receptors. Thus, we suggested the usefulness of the combined treatment with an H1 antagonist and an H4 antagonist for the suppression of atopic dermatitis.
AB - 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 immediatephase 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 H1 receptors and the late-phase swelling via H3/H4 receptors. Thus, we suggested the usefulness of the combined treatment with an H1 antagonist and an H4 antagonist for the suppression of atopic dermatitis.
KW - 12-O-tetradecanoylphorbol 13-acetate
KW - Allergic dermatitis
KW - Allergic inflammation
KW - Histamine
KW - Picryl chloride
KW - Thymic stromal lymphopoietin
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U2 - 10.1254/jphs.09R03FM
DO - 10.1254/jphs.09R03FM
M3 - Article
C2 - 19609061
AN - SCOPUS:67749111697
VL - 110
SP - 245
EP - 250
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
SN - 1347-8648
IS - 3
ER -