NMI and IFP35 serve as proinflammatory DAMPs during cellular infection and injury.
NMI and IFP35 serve as proinflammatory DAMPs during cellular infection and injury.
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NMI 和 IFP35 在细胞感染和损伤期间充当促炎性 DAMP。
DOI：
10.1038/s41467-017-00930-9
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发表时间：
2017-10-16
影响因子：
16.6
通讯作者：
Liang H
中科院分区：
文献类型：
--
作者：
Xiahou Z;Wang X;Shen J;Zhu X;Xu F;Hu R;Guo D;Li H;Tian Y;Liu Y;Liang H
损伤相关分子模式（DAMP）触发先天免疫反应并加剧炎症以对抗感染和细胞损伤。因此，识别DAMPs并揭示其功能至关重要。在这里，我们报告了两种分子，N-myc和STAT相互作用（NMI）和干扰素诱导的蛋白35（IFP 35）作为DAMP，并在脂多糖诱导的脓毒性休克或对乙酰氨基酚诱导的肝损伤过程中由活化的巨噬细胞释放。我们发现细胞外NMI和IFP 35通过Toll样受体4途径激活核因子-κB，激活巨噬细胞释放促炎细胞因子。此外，NMI的血清水平在死于严重炎症的患者中增加。NMI缺乏降低败血症和肝损伤小鼠模型的炎症反应和死亡率。因此，我们提出细胞外NMI和IFP 35作为DAMP加剧炎症，使其成为临床干预的潜在治疗靶点。
Damage-associated molecular patterns (DAMP) trigger innate immune response and exacerbate inflammation to combat infection and cellular damage. Identifying DAMPs and revealing their functions are thus of crucial importance. Here we report that two molecules, N-myc and STAT interactor (NMI) and interferon-induced protein 35 (IFP35) act as DAMPs and are released by activated macrophages during lipopolysaccharide-induced septic shock or acetaminophen-induced liver injury. We show that extracellular NMI and IFP35 activate macrophages to release proinflammatory cytokines by activating nuclear factor-κB through the Toll-like receptor 4 pathway. In addition, the serum levels of NMI are increased in patients who succumbed to severe inflammation. NMI deficiency reduces inflammatory responses and mortality in mouse models of sepsis and liver injury. We therefore propose that extracellular NMI and IFP35 exacerbate inflammation as DAMPs, making them potential therapeutic targets for clinical intervention.
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影响因子：
24.1
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