Linked Life Data

21248248

Source:http://linkedlifedata.com/resource/pubmed/id/21248248

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-2-3
pubmed:abstractText
Toll-like receptors are a group of pattern-recognition receptors that play a crucial role in "danger" recognition and induction of the innate immune response against bacterial and viral infections. TLR3 has emerged as a key sensor of viral dsRNA, resulting in the induction of the anti-viral molecule, IFN-?. Thus, a clearer understanding of the biological processes that modulate TLR3 signaling is essential. Previous studies have shown that the TLR adaptor, Mal/TIRAP, an activator of TLR4, inhibits TLR3-mediated IFN-? induction through a mechanism involving IRF7. In this study, we sought to investigate whether the TLR adaptor, MyD88, an activator of all TLRs except TLR3, has the ability to modulate TLR3 signaling. Although MyD88 does not significantly affect TLR3 ligand-induced TNF-? induction, MyD88 negatively regulates TLR3-, but not TLR4-, mediated IFN-? and RANTES production; this process is mechanistically distinct from that employed by Mal/TIRAP. We show that MyD88 inhibits IKK?-, but not TBK1-, induced activation of IRF3. In doing so, MyD88 curtails TLR3 ligand-induced IFN-? induction. The present study shows that while MyD88 activates all TLRs except TLR3, MyD88 also functions as a negative regulator of TLR3. Thus, MyD88 is essential in restricting TLR3 signaling, thereby protecting the host from unwanted immunopathologies associated with the excessive production of IFN-?. Our study offers a new role for MyD88 in restricting TLR3 signaling through a hitherto unknown mechanism whereby MyD88 specifically impairs IKK?-mediated induction of IRF3 and concomitant IFN-? and RANTES production.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
186
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2514-22
pubmed:meshHeading
pubmed-meshheading:21248248-Animals, pubmed-meshheading:21248248-Cell Line, pubmed-meshheading:21248248-Chemokine CCL5, pubmed-meshheading:21248248-Down-Regulation, pubmed-meshheading:21248248-HEK293 Cells, pubmed-meshheading:21248248-Humans, pubmed-meshheading:21248248-I-kappa B Kinase, pubmed-meshheading:21248248-Interferon Regulatory Factor-3, pubmed-meshheading:21248248-Interferon-beta, pubmed-meshheading:21248248-Mice, pubmed-meshheading:21248248-Mice, 129 Strain, pubmed-meshheading:21248248-Mice, Inbred C57BL, pubmed-meshheading:21248248-Mice, Knockout, pubmed-meshheading:21248248-Myeloid Differentiation Factor 88, pubmed-meshheading:21248248-Phosphorylation, pubmed-meshheading:21248248-Signal Transduction, pubmed-meshheading:21248248-Toll-Like Receptor 3, pubmed-meshheading:21248248-Up-Regulation
pubmed:year
2011
pubmed:articleTitle
Absence of MyD88 results in enhanced TLR3-dependent phosphorylation of IRF3 and increased IFN-? and RANTES production.
pubmed:affiliation
Department of Biology, Institute of Immunology, National University of Ireland Maynooth, Maynooth, County Kildare, Ireland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't