Overproduction of Th2-specific chemokines in NC/Nga mice exhibiting atopic dermatitis-like lesions

被引:353
作者
Vestergaard, C
Yoneyama, H
Murai, M
Nakamura, K
Tamaki, K
Terashima, Y
Imai, T
Yoshie, O
Irimura, T
Mizutani, H
Matsushima, K
机构
[1] Univ Tokyo, Sch Med, Dept Mol Prevent Med, Bunkyo Ku, Tokyo 1130033, Japan
[2] Univ Aarhus, Marselisborg Hosp, Dept Dermatol, Aarhus 8000 C, Denmark
[3] Univ Tokyo, Sch Med, Dept Dermatol, Tokyo 1130033, Japan
[4] Kinki Univ, Sch Med, Dept Bacteriol, Osaka 5898511, Japan
[5] Univ Tokyo, Grad Sch Pharmacol, Lab Canc Biol & Mol Immunol, Tokyo 1130033, Japan
[6] Mie Univ, Fac Med, Dept Dermatol, Tsu, Mie 5478507, Japan
关键词
D O I
10.1172/JCI7613
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
We have examined the expression of chemokines and their receptors in the atopic dermatitis-like (AD-like) lesions of NC/Nga mice. Such lesions develop when the mice are kept in conventional conditions, but not when they are kept isolated from specific pathogens. The thymus- and activation-regulated chemokine TARC is unexpectedly highly expressed in the basal epidermis of 14-week-old mice with lesions, whereas it is not expressed in the skin without lesions. Production of TARC by keratinocytes was confirmed by culturing murine keratinocytic cell line cells (PAM212) with TNF-alpha, IFN-gamma, or IL-1 beta. Expression of another Th2 chemokine, macrophage-derived chemokine (MDC), was observed in the skin from mice kept in both conventional and pathogen-free conditions, but expression of MDC was increased severalfold in the skin with lesions. The cellular origin of MDC was identified to be dermal dendritic cells. Infiltration of the skin by IL-4-producing T cells and mast cells, and the increase of CCR4 mRNA in the skin, coincided with the development of AD lesions. These observations indicate that TARC and MDC actively participate in the pathogenesis of AD-like lesions in NC/Nga mice and that these Th2 chemokines could be novel targets for intervention therapy of AD in humans.
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收藏
页码:1097 / 1105
页数:9
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