| The toll-like receptor 9 agonist, CpG-oligodeoxynucleotide 1826, ameliorates cardiac dysfunction after trauma-hemorrhage. | |
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MedLine Citation:
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PMID: 22576005 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Xia Zhang; Ming Gao; Tuanzhu Ha; John H Kalbfleisch; David L Williams; Chuanfu Li; Race L Kao |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Shock (Augusta, Ga.) Volume: 38 ISSN: 1540-0514 ISO Abbreviation: Shock Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-07-18 Completed Date: 2012-10-18 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 9421564 Medline TA: Shock Country: United States |
Other Details:
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Languages: eng Pagination: 146-52 Citation Subset: IM |
Affiliation:
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Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City 37614, Tennessee, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adjuvants, Immunologic
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pharmacology* Animals Chromones / pharmacology Disease Models, Animal Enzyme Inhibitors / pharmacology Heart Diseases / prevention & control* Hemorrhage / complications* Hypotension / prevention & control* MAP Kinase Signaling System / drug effects Male Mice 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 | |
ID/Acronym/Agency:
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GM083016/GM/NIGMS NIH HHS; GM093878/GM/NIGMS NIH HHS; GM53522/GM/NIGMS NIH HHS; HL071837/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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 2.7.1.137/Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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