Advantages of histamine H4 receptor antagonist usage with H1 receptor antagonist for the treatment of murine allergic contact dermatitis
Advantages of histamine H4 receptor antagonist usage with H1 receptor antagonist for the treatment of murine allergic contact dermatitis
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DOI：
10.1111/j.1600-0625.2012.01559.x
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发表时间：
2012-09-01
影响因子：
3.6
通讯作者：
Ohtsu, Hiroshi
中科院分区：
文献类型：
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作者：
Matsushita, Ayuko;Seike, Masahiro;Ohtsu, Hiroshi
溃疡性皮炎（UD）是一种病因不明的严重炎症性皮肤病。最近，胰岛素受体底物1 KO小鼠被证明对UD具有完全抗性。在这项研究中，我们发现高脂肪饮食（HFD）喂养显著增加野生型（WT） C57BL/6小鼠UD的发生率，锂介导的gsk3 - β抑制也是如此，gsk3 - β是IRS1的关键负调节因子。与WT小鼠相比，hfd喂养的Irs1-KO小鼠对UD的抗性完全保留。我们的研究结果确定IRS1是UD发病机制的关键决定因素，并在饮食组成、肥胖诱导的炎症和慢性溃疡之间建立了直接联系。
Ulcerative dermatitis (UD) is a severe inflammatory skin disorder with an unknown aetiology. Recently, insulin receptor substrate 1 KO mice were shown to be fully resistant to UD. In this study, we showed that high-fat diet (HFD) feeding significantly increased incidence of UD in wild type (WT) C57BL/6 mice, as did lithium-mediated inhibition of GSK3-beta, which is a key negative regulator of IRS1. In contrast to WT mice, resistance to UD was fully preserved in HFD-fed Irs1-KO mice. Our results identify IRS1 as a key determinant of UD pathogenesis and establish a direct link between diet composition, obesity-induced inflammation and chronic ulceration.