Rho-kinase signalling in systemic inflammatory responses
Author
Summary, in English
Rho-kinase is an effector enzyme of small Rho-GTPases which are ubiquitously expressed and mediate a variety of intracellular mechanisms. Most importantly, Rho-kinase is involved in the organization of the actin cytoskeleton and cell movement. Further, it is known to be involved in the regulation of innate immunity. Thus, we herein investigated the involvement of Rho-kinase in endotoxemic liver and lung injury in a model of systemic inflammatory reaction. Further, we investigated the potential effects of simvastatin on LPS-induced liver injury, knowing that HMG-CoA reductase substrates are required for Rho-kinase activation.
We found that Rho-kinase is centrally involved in the regulation of inflammatory responses in endotoxemic systemic inflammation-induced liver and lung injury. Further, Rho-kinase also mediates local inflammatory reaction in the lung. HMG-CoA reductase inhibition was further shown to effectively prevent endotoxemic liver injury.
Thus, we herein propose Rho-kinase as an attractive target for treatment and prevention of endotoxin-induced inflammatory organ injury.
Department/s
Publishing year
2012
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2012:80
Document type
Dissertation
Publisher
Department of Clinical Sciences, Lund University
Topic
- Surgery
Status
Published
Research group
- Surgery
Supervisor
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-87189-43-2
Defence date
9 October 2012
Defence time
08:00
Defence place
CRC, Entrance 72, Skåne University Hospital, Malmö
Opponent
- Rene H. Tolba (Prof. Dr.)