Document Detail


Systemic inflammation and liver injury following hemorrhagic shock and peripheral tissue trauma involve functional TLR9 signaling on bone marrow-derived cells and parenchymal cells.
MedLine Citation:
PMID:  20577143     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hemorrhagic shock due to trauma (HS/T) induces an inflammatory response that can contribute to end-organ injury. The pathways involved in the initiation and propagation of HS/T-induced inflammation are incompletely understood. Here, we hypothesized that the DNA sensor TLR9 would have a role in inflammatory signaling after HS/T. Using mice expressing a nonfunctional, mutant form of TLR9, we identified a role of TLR9 in driving the initial cytokine response and liver damage in a model of hemorrhagic shock and bilateral femur fracture. Circulating DNA levels were found to correlate with the degree of tissue damage. Experiments using chimeric mice show that TLR9 on both bone marrow-derived cells and parenchymal cells are important for the TLR9-mediated liver and tissue damage, as well as systemic inflammation after HS/T. These data suggest that release of DNA may be a driver of the inflammatory response to severe injury as well as a marker of the extent of tissue damage. One of the sensors of DNA in the setting of HS/T seems to be TLR9.
Authors:
Roop Gill; Xiangcai Ruan; Christoph L Menzel; Seung Namkoong; Patricia Loughran; David J Hackam; Timothy R Billiar
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  35     ISSN:  1540-0514     ISO Abbreviation:  Shock     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-03     Completed Date:  2011-04-25     Revised Date:  2012-02-02    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  164-70     Citation Subset:  IM    
Affiliation:
Department of Surgery, University of Pittsburgh, 200 Lothrop St., Pittsburgh, PA 15213, USA. billiartr@upmc.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Marrow Cells / metabolism*
Inflammation / genetics,  metabolism
Liver / injuries,  metabolism
Mice
Mice, Mutant Strains
Shock, Hemorrhagic / genetics,  metabolism*
Signal Transduction*
Toll-Like Receptor 9 / genetics,  metabolism*
Wounds and Injuries / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
GM-53789-09/GM/NIGMS NIH HHS; P50 GM053789-090007/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Tlr9 protein, mouse; 0/Toll-Like Receptor 9

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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