Physiologic role of ubiquitin after severe tissue trauma

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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.