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.Damage-associated molecular patterns (DAMP) are important mediators of innate immunity. Here the authors show that N-myc and STAT interactor (NMI) and interferon-induced protein 35 (IFP35) act as DAMPs to promote inflammation by activating macrophages via the Toll-like receptor 4 and NF-κB pathways.

中文翻译：

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NMI和IFP35在细胞感染和损伤期间充当促炎性DAMP。

损伤相关分子模式（DAMP）触发先天免疫反应并加剧炎症以抵抗感染和细胞损伤。因此，识别DAMP并揭示其功能至关重要。在这里，我们报告两个分子，N-myc和STAT相互作用物（NMI）和干扰素诱导的蛋白35（IFP35）充当DAMPs，并在脂多糖诱导的败血性休克或对乙酰氨基酚引起的肝损伤期间被活化的巨噬细胞释放。我们显示细胞外NMI和IFP35激活巨噬细胞，通过Toll样受体4途径激活核因子-κB释放促炎细胞因子。此外，死于严重炎症的患者血清NMI升高。NMI缺乏会降低脓毒症和肝损伤小鼠模型的炎症反应并降低其死亡率。因此，我们建议细胞外NMI和IFP35作为DAMPs加剧炎症，使其成为临床干预的潜在治疗靶点。损伤相关分子模式（DAMP）是先天免疫的重要介质。在这里，作者表明N-myc和STAT相互作用因子（NMI）和干扰素诱导的蛋白35（IFP35）充当DAMP，通过Toll样受体4和NF-κB途径激活巨噬细胞来促进炎症。