Document Detail


Cutting edge: TLR4 deficiency confers susceptibility to lethal oxidant lung injury.
MedLine Citation:
PMID:  16210584     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
TLRs have been studied extensively in pathogen-mediated host responses. We use a murine model of lethal oxidant-mediated injury to demonstrate for the first time that mammalian TLR4 is required for survival and lung integrity. Administering high levels of inspired oxygen, or hyperoxia, is commonly used as a life-sustaining measure in critically ill patients. However, prolonged exposures can lead to respiratory failure and death. TLR4-deficient mice exhibited increased mortality and lung injury during hyperoxia. The enhanced susceptibility of TLR4-deficient mice to hyperoxia was associated with an inability to up-regulate Bcl-2 and phospho-Akt. Restoration of Bcl-2 and phospho-Akt levels by the exogenous transfer of the antioxidant gene heme oxygenase-1 markedly attenuated hyperoxia-induced injury, apoptosis, and mortality in TLR4-deficient mice. Taken together, our results suggest a protective role of TLR4 in oxidant-mediated injury, providing novel mechanistic links among innate immunity, oxidant stress, and apoptosis.
Authors:
Xuchen Zhang; Peiying Shan; Salman Qureshi; Robert Homer; Ruslan Medzhitov; Paul W Noble; Patty J Lee
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  175     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-10-07     Completed Date:  2005-12-13     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4834-8     Citation Subset:  AIM; IM    
Affiliation:
Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / physiology*
Gene Transfer Techniques
Genetic Predisposition to Disease*
Heme Oxygenase-1 / genetics,  metabolism
Hyperoxia / metabolism,  mortality
Lung / metabolism*,  pathology*
Mice
Mice, Knockout
Oxidants / toxicity*
Toll-Like Receptor 4 / deficiency*,  genetics*,  physiology
Grant Support
ID/Acronym/Agency:
HL071595/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Oxidants; 0/Tlr4 protein, mouse; 0/Toll-Like Receptor 4; EC 1.14.99.3/Heme Oxygenase-1
Comments/Corrections
Comment In:
J Immunol. 2006 Apr 1;176(7):3856-7; author reply 3857   [PMID:  16547213 ]
Erratum In:
J Immunol. 2005 Dec 15;175(12):8440

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


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