Bacterial translocation in Sepsis: Role of hypoxia regulated gene expression

• Applicant: Dr. Jörn Andreas Karhausen
• Subject Area: Anaesthesiology
• Term: from 2005 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5457024

The gastrointestinal tract is supported by a rich and complex underlying vasculature. As a consequence the intestinal epithelial cell-layer is particularly susceptible to damage associated with diminished blood flow. In various diseases, such as sepsis this fragile equilibrium is fundamentally challenged both through increase of metabolic rate and the decrease of intestinal perfusion characteristically associated with the condition. Although other factors also play a role under such circumstances, a primary consequence is that of epithelial tissue hypoxia. Under hypoxic conditions, barrier function and thus sustained control over the flux of potentially harmfull luminal xenobiotics seems to be maintained to a certain degree by compensatory mechanisms. Representing a novel, innate mechanism that may guard immunologic components of the lamina propria from exposure to pathogenic luminal bacteria, proinflammatory molecules and toxins, we have established hypoxia inducible factor (HIF) regulated expression of barrier relevant genes as a protective influence in a model disease of inflammation. Completion of the aims outlined in this proposal will yield insight into the regulatory mechanisms of epithelial barrier function in sepsis and clarify compensatory responses designed to preserve the barrier integrity that may prove valuable in development of novel therapeutic concepts.

• DFG Programme: Research Grants