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

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  • Hirasawa Noriyasu
    Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan
  • Ohsawa Yuhsuke
    Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan
  • Ishihara Kenji
    Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan Department of Bioengineering and Robotics, Graduate School of Engineering, Tohoku University, Japan
  • Seyama Toshio
    Laboratory of Life Sciences, Faculty Pharmacy, Yasuda Women’s University, Japan
  • Hong JangJa
    Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan Laboratory of Life Sciences, Faculty Pharmacy, Yasuda Women’s University, Japan
  • Ohuchi Kazuo
    Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan Laboratory of Life Sciences, Faculty Pharmacy, Yasuda Women’s University, Japan

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  • 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

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Abstract

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 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.<br>

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