Physiologic role of ubiquitin after severe tissue trauma

泛素是存在于所有真核细胞中的高度保守的热稳定的76个氨基酸（8.6kDa）蛋白，其在多种细胞功能中具有已知的重要作用，主要在泛素-蛋白酶体途径内。最近的研究表明，细胞内泛素在免疫反应的调节和炎症诱导的代谢变化中起着至关重要的作用。我们自己的体外和体内数据表明，细胞外遍在蛋白本身作为细胞因子样介质，在创伤和败血症后具有抗炎特性。总之，这些关键的初步数据支持的核心假设，泛素是一个关键的生理介质/炎症和代谢反应与严重创伤的调制器。我们计划通过选定的体外和体内实验来评估这一假设，这些实验旨在回答与释放和作用机制、免疫学和代谢特性、生物学意义和预后价值相关的基本问题。总之，这些数据可以从根本上揭示严重组织创伤发病机制的新信息。

Ubiquitin is a highly conserved heat stable 76 amino acid (8.6 kDa) protein present in all eukaryotic cells with known essential roles in multiple cell functions, mostly within the ubiquitin-proteasome pathway. Recent findings implicated intracellular ubiquitin to play a crucial role in regulation of immunological responses and in inflammation induced metabolic changes. Our own in-vitro and in-vivo data showed that extracellular ubiquitin itself acts as a cytokine-like mediator with anti-inflammatory properties after trauma and sepsis. Altogether, these critical preliminary data support the central hypothesis that ubiquitin is a key physiologic mediator/modulator of inflammatory and metabolic responses associated with severe trauma. We plan to evaluate this hypothesis with selected in-vitro and in-vivo experiments designed to answer fundamental questions related to mechanism of release and action, immunological and metabolic properties, biological significance and prognostic value. Altogether these data could reveal fundamentally new information about the pathogenesis of severe tissue trauma.