Methods of Modulating Inflammatory Reactions by Modulating Xanthine Oxidoreductase Activity
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    发明申请
    Methods of Modulating Inflammatory Reactions by Modulating Xanthine Oxidoreductase Activity 审中-公开
    通过调节黄嘌呤氧化还原酶活性来调节炎症反应的方法

    公开(公告)号:US20070224287A1

    公开(公告)日:2007-09-27

    申请号:US10573354

    申请日:2004-09-27

    IPC分类号: A61K31/519 A61K33/24 C12N9/02

    摘要: Evidence is presented that inflammation and injury involves activation of xanthine oxidoreductase (XOR) in the newly recruited mononuclear phagocytes (MNP). XOR has been shown to be increased predominantly in the MNP that increase rapidly in the lungs of rats that develop acute lung injury (ALI) following intratracheal cytokine insufflation. XOR was recovered from the MNP largely converted to its oxygen radical generating, reversible O-form, and alveolar MNP exhibited increased oxidative stress as evidenced by increased nitrotyrosine staining. Cytokine insufflation also increased alveolar cell apoptosis. A functional role for XOR in cytokine induced inflammation was demonstrated. Tungsten and allopurinol decreased MNP XOR induction, nitrotyrosine staining, inflammatory cell infiltration, and alveolar cell apoptosis. Transfer of control or allopurinol treated MNP into rat lungs and confirmed a specific role for MNP XOR in promoting lung inflammation. These data indicate that XOR can contribute to lung inflammation by its expression and conversion in a highly mobile inflammatory cell population.

    摘要翻译: 证据表明炎症和损伤涉及新招募的单核吞噬细胞(MNP)中黄嘌呤氧化还原酶(XOR)的活化。 已显示XOR主要在MNP中增加,其在气管内细胞因子吹入后发展为急性肺损伤(ALI)的大鼠肺中迅速增加。 通过增加的硝基酪氨酸染色证明,从MNP中回收的XOR大部分转化为其产生氧自由基的可逆O型,并且肺泡MNP显示增加的氧化应激。 细胞因子注入也增加肺泡细胞凋亡。 证明了XOR在细胞因子诱导炎症中的功能作用。 钨和别嘌醇降低MNP XOR诱导,硝基酪氨酸染色,炎症细胞浸润和肺泡细胞凋亡。 将对照或别嘌呤醇治疗的MNP转移到大鼠肺中,并确认MNP XOR在促进肺部炎症中的特异性作用。 这些数据表明XOR可以通过其在高度流动的炎性细胞群体中的表达和转化来促进肺部炎症。