National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
Nat Commun. 2017 Oct 16;8(1):950. doi: 10.1038/s41467-017-00930-9.
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.
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，鉴定 DAMP 并揭示其功能至关重要。在这里，我们报告说，两种分子，N- myc 和 STAT 相互作用因子（NMI）和干扰素诱导蛋白 35（IFP35）作为 DAMP，并在脂多糖诱导的败血症休克或对乙酰氨基酚诱导的肝损伤期间由激活的巨噬细胞释放。我们表明，细胞外 NMI 和 IFP35 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，在死于严重炎症的患者中，血清 NMI 水平升高。NMI 缺乏可减少败血症和肝损伤小鼠模型中的炎症反应和死亡率。因此，我们提出细胞外 NMI 和 IFP35 作为 DAMP 加剧炎症，使其成为临床干预的潜在治疗靶点。
