Document Detail


Unexpected protective role for Toll-like receptor 3 in the arterial wall.
MedLine Citation:
PMID:  21220319     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The critical role of Toll-like receptors (TLRs) in mammalian host defense has been extensively explored in recent years. The capacity of about 10 TLRs to recognize conserved patterns on many bacterial and viral pathogens is remarkable. With so few receptors, cross-reactivity with self-tissue components often occurs. Previous studies have frequently assigned detrimental roles to TLRs, in particular to TLR2 and TLR4, in immune and cardiovascular disease. Using human and murine systems, we have investigated the consequence of TLR3 signaling in vascular disease. We compared the responses of human atheroma-derived smooth muscle cells (AthSMC) and control aortic smooth muscle cells (AoSMC) to various TLR ligands. AthSMC exhibited a specific increase in TLR3 expression and TLR3-dependent functional responses. Intriguingly, exposure to dsRNA in vitro and in vivo induced increased expression of both pro- and anti-inflammatory genes in vascular cells and tissues. Therefore, we sought to assess the contribution of TLR3 signaling in vivo in mechanical and hypercholesterolemia-induced arterial injury. Surprisingly, neointima formation in a perivascular collar-induced injury model was reduced by the systemic administration of the dsRNA analog Poly(I:C) in a TLR3-dependent manner. Furthermore, genetic deletion of TLR3 dramatically enhanced the development of elastic lamina damage after collar-induced injury. Accordingly, deficiency of TLR3 accelerated the onset of atherosclerosis in hypercholesterolemic ApoE(-/-) mice. Collectively, our data describe a protective role for TLR signaling in the vessel wall.
Authors:
Jennifer E Cole; Tina J Navin; Amanda J Cross; Michael E Goddard; Lena Alexopoulou; Anuja T Mitra; Alun H Davies; Richard A Flavell; Marc Feldmann; Claudia Monaco
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-01-10
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  108     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-09     Completed Date:  2011-03-30     Revised Date:  2013-07-02    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2372-7     Citation Subset:  IM    
Affiliation:
Kennedy Institute of Rheumatology, Faculty of Medicine, Imperial College, London W6 8LH, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Animals
Carotid Arteries / metabolism*,  pathology
Carotid Artery Diseases / metabolism*,  pathology
Female
Humans
Hypercholesterolemia / metabolism,  pathology
Interferon Inducers / pharmacology
Male
Mice
Mice, Knockout
Muscle, Smooth, Vascular / metabolism*,  pathology
Myocytes, Smooth Muscle / metabolism*,  pathology
Poly I-C / pharmacology
Signal Transduction*
Toll-Like Receptor 3 / agonists,  genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
//Arthritis Research UK
Chemical
Reg. No./Substance:
0/Interferon Inducers; 0/TLR3 protein, human; 0/TLR3 protein, mouse; 0/Toll-Like Receptor 3; 24939-03-5/Poly I-C
Comments/Corrections
Comment In:
Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2637-8   [PMID:  21292987 ]

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


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