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Targeting the ubiquitin proteasome pathway for the treatment of septic shock in patients

Jan Brun3,1,2 and Douglas A Gray1,2*

Author Affiliations

1 Ottawa Health Research Institute, Ottawa, ON, Canada K1Y 4E9

2 Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada K1H 8M5

3 Apoptosis Research Centre, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada K1H 8L1

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Critical Care 2009, 13:311 doi:10.1186/cc7946

Published: 14 August 2009

Abstract

Endotoxic shock is a serious systemic inflammatory response to an external biological stressor. The responsiveness of NF-κB is built upon rapid protein modification and degradation involving the ubiquitin proteasome pathway. Using transgenic mice, we have obtained in vivo evidence that interference with this pathway can alleviate the symptoms of toxic shock. We posit that administration of proteasome inhibitors may enhance the survival of patients with septic shock.