Epithelial HIF and NFKB regulation during hypoxia and inflammation

• Applicant: Privatdozent Dr. Stefan Ehrentraut
• Subject Area: Anaesthesiology
• Term: from 2010 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 164742913

Hypoxia and inflammation often occur concomitantly, and together lead to profound changes in tissue metabolism. Such “inflammatory hypoxia” results, at least in part, from active recruitment of energy and oxygen demanding inflammatory cell types. Several studies implicate an important role of extracellular Adenosine (Ado) in tissue protection during hypoxia. Studies addressing regulation of HIF-1α and NFκB revealed that Ado activates HIF- 1α and inhibits NFκB through direct post-translational modifications (deneddylation). We therefore hypothesize that Ado functions as an endogenous anti-inflammatory by Cullin deneddylation. The aim of this proposal is to 1) elucidate mechanisms of Ado-mediated Cullin deneddylation in the epithelium, 2) identify targets of Ado-induced anti-inflammatory actions mediated by Cullin deneddylation, and 3) determine, whether pharmacological stabilization of HIF-1α might serve as a suitable therapeutic target during inflammation and hypoxia in vivo. These experiments will facilitate significant progress on a more basic understanding of inflammatory response during hypoxia. Additionally, pharmacological approaches to inflammatory disease contributing to several different fields of medicine will be made.

• DFG Programme: Research Fellowships
• International Connection: USA
• Hosts: Professor Sean Colgan, Ph.D.; Professor Holger Klaus Eltzschig, Ph.D.