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

Noriyasu Hirasawa; Yuhsuke Ohsawa; Kenji Ishihara; Toshio Seyama; JangJa Hong; Kazuo Ohuchi

doi:10.1254/jphs.09R03FM

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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

Noriyasu Hirasawa, Yuhsuke Ohsawa, Kenji Ishihara, Toshio Seyama, JangJa Hong, Kazuo Ohuchi

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

Keywords: allergic dermatitis, histamine, picryl chloride, 12-O-tetradecanoylphorbol 13-acetate, thymic stromal lymphopoietin, allergic inflammation

JOURNAL FREE ACCESS

2009 Volume 110 Issue 3 Pages 245-250

DOI https://doi.org/10.1254/jphs.09R03FM

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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.

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