Document Detail

The toll-like receptor 9 agonist, CpG-oligodeoxynucleotide 1826, ameliorates cardiac dysfunction after trauma-hemorrhage.
MedLine Citation:
PMID:  22576005     Owner:  NLM     Status:  MEDLINE    
Cardiovascular collapse is the major factor contributing to the mortality of trauma-hemorrhage (T-H) patients. Toll-like receptors (TLRs) play a critical role in T-H-induced cardiac dysfunction. This study evaluated the role of TLR9 agonist, CpG-oligodeoxynucleotide (ODN) 1826, in cardiac functional recovery after T-H. Trauma-hemorrhage was induced in a murine model by soft tissue injury and blood withdrawals from the jugular vein to a mean arterial pressure of 35 ± 5 mmHg. Mice were treated with CpG-ODN 1826 (10 μg/30 g body weight) by intraperitoneal injection 1 h before T-H (n = 5-8/group). Hemodynamic parameters were measured before, during hemorrhage, and at 60 min after T-H. Trauma-hemorrhage significantly decreased the mean arterial pressure and left ventricular pressure compared with sham controls. In contrast, CpG-ODN administration significantly attenuated the decrease in arterial pressure and left ventricular pressure due to T-H. Trauma-hemorrhage markedly decreased myocardial levels of phosphorylated Akt by 57.9%. However, CpG-ODN treatment significantly blunted the decrement in phospho-Akt by activating the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. The PI3K inhibitor LY294002 partially abolished CpG-induced cardioprotection, indicating that additional signaling pathways are involved in the protective effect of CpG-ODN after T-H. We observed that CpG-ODN treatment also significantly attenuated the decrease in myocardial phospho-ERK levels after T-H. Inhibition of ERK by U0126 also partially abolished the cardioprotective effect of CpG-ODN after T-H. Our data suggest that CpG-ODN significantly attenuates T-H-induced cardiac dysfunction. The mechanisms involve activation of both PI3K/Akt and ERK signaling pathways. The TLR9 agonist, CpG-ODN 1826, may provide a novel treatment strategy for preventing or managing cardiac dysfunction and enhancing recovery in T-H patients.
Xia Zhang; Ming Gao; Tuanzhu Ha; John H Kalbfleisch; David L Williams; Chuanfu Li; Race L Kao
Related Documents :
12745915 - Respiratory effect on the pulse spectrum.
11194615 - Effect of seated posture on interface pressure in children who are able-bodied and who ...
24867405 - The role of dural sinus stenosis in idiopathic intracranial hypertension pathogenesis. ...
23188295 - Sensing characteristics of the rocking filters in microstructured fibers optimized for ...
17339265 - Plasma matrix metalloproteinase-9 and left ventricular remodelling after acute myocardi...
18204315 - Effects of intra-aortic counterpulsation on aortic wall energetics and damping: in vivo...
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:  38     ISSN:  1540-0514     ISO Abbreviation:  Shock     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-18     Completed Date:  2012-10-18     Revised Date:  2013-08-14    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  146-52     Citation Subset:  IM    
Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City 37614, Tennessee, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Adjuvants, Immunologic / pharmacology*
Chromones / pharmacology
Disease Models, Animal
Enzyme Inhibitors / pharmacology
Heart Diseases / prevention & control*
Hemorrhage / complications*
Hypotension / prevention & control*
MAP Kinase Signaling System / drug effects
Mice, Inbred C57BL
Morpholines / pharmacology
Oligodeoxyribonucleotides / pharmacology*
Phosphatidylinositol 3-Kinase / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Soft Tissue Injuries / complications*
Toll-Like Receptor 9 / agonists*
Grant Support
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/Chromones; 0/CpG ODN 1826; 0/Enzyme Inhibitors; 0/Morpholines; 0/Oligodeoxyribonucleotides; 0/Toll-Like Receptor 9; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; EC 3-Kinase; EC Proteins c-akt

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

Previous Document:  C1-Inhibitor Suppresses the Endotoxic Activity of a Wide Range of Lipopolysaccharides and Interacts ...
Next Document:  Dietary Phosphatidylcholine Supplementation Attenuates Inflammatory Mucosal Damage in a Rat Model of...