A CCR4 antagonist ameliorates atopic dermatitis-like skin lesions induced by dibutyl phthalate and a hydrogel patch containing ovalbumin

Biomedicine & Pharmacotherapy

Ying-Shu Quan¹  Fumio Kamiyama¹  Akira Kawada²  Naoki Oiso²  Kenji Kabashima³  Kazuhiko Matsuo⁴  Takashi Nakayama⁴  Shota Hatanaka⁴  Yuta Kimura⁴  Keiji Nishiwaki⁵  Yuta Hara⁶ 

[1] CosMED Pharmaceutical Co Ltd, 32 Higashikujokawanishi-cho, Minami-ku, Kyoto, Japan;Department of Dermatology, Kindai University, Faculty of Medicine, 377-2 Ohnohigashi, Osaka-sayama, Osaka, Japan;Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan;Division of Chemotherapy, Kindai University, Faculty of Pharmacy, Kowakae 3-4-1, Higashi-Osaka, Osaka 577-8502, Japan;Division of Computational Drug Design and Discovery, Kindai University, Faculty of Pharmacy, Kowakae 3-4-1, Higashi-Osaka, Osaka 577-8502, Japan;Laboratory of Cell Biology, Kindai University, Faculty of Pharmacy, Kowakae 3-4-1, Higashi-Osaka, Osaka 577-8502, Japan;

关键词: CCR4;    CCL17;    CCL22;    TSLP;    Atopic dermatitis;    Dibutyl phthalate;   

DOI  :  

来源: DOAJ

【 摘 要 】

CCR4 is a chemokine receptor highly expressed by Th2 cells, and regarded as a potential therapeutic target for atopic dermatitis (AD). CCL17 and CCL22 are the CCR4 ligands, and thymic stromal lymphopoietin (TSLP) is shown to promote the expression of CCL17 and CCL22 by dendritic cells. Here, by using dibutyl phthalate (DBP), a TSLP inducer, and a hydrogel patch as a transcutaneous delivery device for ovalbumin, we developed a novel murine AD model and investigated the effect of Compound 22, a CCR4 antagonist. We first found that the mRNA expression of TSLP together with CCL17 and CCL22 was increased in the skins treated with DBP. Furthermore, the topical application of ovalbumin and DBP efficiently and rapidly induced AD-like skin lesions in BALB/c mice, which were characterized by ear swelling accompanied by infiltration of eosinophils, mast cells, and CCR4-expressing Th2 cells in the skin lesions, and elevated total IgE levels in the sera. Using this AD model, we demonstrated that cutaneous administration of Compound 22 inhibited Th2 cell infiltration and ameliorated the AD-like skin lesions. These results suggest that our AD model could be useful for studying new therapeutic strategies. Collectively, CCR4 antagonists may be a promising approach for treating AD.

【 授权许可】

Unknown