期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 109, 期 -, 页码 1437-1444出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2018.10.194
关键词
CCR4; CCL17; CCL22; TSLP; Atopic dermatitis; Dibutyl phthalate
资金
- Ministry of Education, Culture, Sports, Science and Technology-Supported Program for the Strategic Research Foundation at Private Universities [S1411037]
- Kindai University Fund for Antiaging Center Project
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.
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