损伤相关分子模式（Damage-Associated Molecular Pattern, DAMP），也被称为危险信号分子，可以被激活的免疫细胞主动释放，激活周围的内皮细胞或者免疫细胞，并促进它们的增殖和分化，从而起到调控炎症反应的作用，但是目前其释放机制仍不清楚。本项目拟以申请人发现的一类新型DAMP分子——IFP35（Interferon-Induced Protein 35kD）家族蛋白为例开展研究。该家族蛋白IFP35和N-Myc结合蛋白（N-Myc-interacting protein, NMI）不含分泌信号肽，但是可以被LPS刺激的巨噬细胞主动释放，发挥促炎作用。我们计划通过研究IFP35和NMI的相互作用蛋白，寻找其释放途径，并通过解析IFP35，NMI及IFP35/NMI复合物的结构，研究其释放过程中的调节机制。项目研究结果可以促进人们对DAMP释放机制的理解。

Damage-Associated Molecular Patterns (DAMP), also known as the dangerous signal molecules (or Alarmin), are important inflammatory regulators. Released by activated immune cells, they stimulate the surrounding endothelial cells or immune cells, and promote their proliferation and differentiation, thereby orchestrating the inflammation responses. The mechanism of DAMP release are still unclear. In this project, we are going to study the release mechanism by studying the IFP35 (interferon-induced protein 35kD) family proteins, which were recently reported as DAMPs by our group. IFP35 and iNMI (N-Myc-interacting protein) do not possess secretory signal peptides. However, they can be actively released by LPS stimulated macrophages as proinflammatory molecule. We propose to examine the release pathway of IFP35 and NMI by studying their interaction proteins, and analyze the regulatory mechanism of its release process by determining the structure of IFP35, NMI and IFP35/NMI complex. Our results would promote the understanding of the secretion mechanism of DAMPs.