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The Atopic Dermatitis-Like Symptoms Induced by MC903 Were Alleviated in JNK1 Knockout Mice
Choi, Jinhwan,Kim, Jong Rhan,Kim, Heejeung,Kim, Yoon A,Lee, Hyong Joo,Kim, Jiyoung,Lee, Ki Won Oxford University Press 2013 Toxicological sciences Vol.136 No.2
<P>Atopic dermatitis (AD) is a common allergic disease, imposing large social and economic burdens worldwide. Atopic dermatitis is characterized by eczematous skin lesions and immunoglobulin E (IgE) hypersecretion. We investigated the role of JNK1 on the development of AD in mice. The vitamin D3 analogue MC903, a psoriasis therapeutic drug, was used to induce AD-like symptoms in wild-type (WT) and JNK1−/− mice. The symptoms of AD were less severe in JNK1−/− mice compared with WT mice. JNK1−/− mice showed less ear thickening and infiltration of eosinophils and mast cells in AD-like lesions than did WT mice when treated with MC903. MC903-treated JNK1−/− mice also showed significantly lower level of serum IgE, which was elevated in MC903-treated WT mice. Splenocytes isolated from MC903-treated WT and JNK1−/− mice were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies. Splenocytes from JNK1−/− mice produced lower levels of T-helper (Th2) cytokines (interleukin-4 and -13) and transcription factor GATA-binding protein 3, and produced increased levels of the Th1 cytokines interferon-γ and transcription factor T-box expressed in T cells. Our results indicate that JNK1 plays an important role in the pathogenesis of AD and may be a useful target for therapies to ameliorate AD.</P>