| 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 |
Related Documents
:
|
22666289 - Analgesic and anti-inflammatory activities of methanol extract of ficus pumila l. in mice. 19584819 - Strategies to modulate immune responses: a new frontier for gene therapy. 11249649 - Clinical applications of dendritic cell vaccines. 19837059 - Immunotherapy of cancer. 22525859 - Anti-inflammatory activity of korean thistle cirsium maackii and its major flavonoid, l... 20515849 - To suppress to rescue? changing the approach for recalling anticancer immune responses. 9250589 - Murine silver-induced autoimmunity: silver shares induction of antinucleolar antibodies... 22726399 - Atheroprotector role of the spleen based on the teaching of avicenna (ibn sina). 15514669 - Lifespan and mitochondrial control of neurodegeneration. |
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: 2011-12-01 |
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. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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
Previous Document: Molecular imaging of active mutant L858R EGF receptor (EGFR) kinase-expressing nonsmall cell lung ca...
Next Document: Bile acid stimulates hepatocyte polarization through a cAMP-Epac-MEK-LKB1-AMPK pathway.