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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2008-10-31
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pubmed:abstractText |
Toll-like receptors (TLRs) can detect endogenous danger molecules released upon tissue injury resulting in the induction of a proinflammatory response. One of the TLR family members, TLR4, is constitutively expressed at RNA level on renal epithelium and this expression is enhanced upon renal ischemia/reperfusion (I/R) injury. The functional relevance of this organ-specific upregulation remains however unknown. We therefore investigated the specific role of TLR4 and the relative contribution of its two downstream signaling cascades, the MyD88-dependent and TRIF-dependent cascades in renal damage by using TLR4-/-, MyD88-/- and TRIF-mutant mice that were subjected to renal ischemia/reperfusion injury. Our results show that TLR4 initiates an exaggerated proinflammatory response upon I/R injury, as reflected by lower levels of chemokines and infiltrating granulocytes, less renal damage and a more preserved renal function in TLR4-/- mice as compared to wild type mice. In vitro studies demonstrate that renal tubular epithelial cells can coordinate an immune response to ischemic injury in a TLR4-dependent manner. In vivo we found that epithelial- and leukocyte-associated functional TLR4 contribute in a similar proportion to renal dysfunction and injury as assessed by bone marrow chimeric mice. Surprisingly, no significant differences were found in renal function and inflammation in MyD88-/- and TRIF-mutant mice compared with their wild types, suggesting that selective targeting of TLR4 directly may be more effective for the development of therapeutic tools to prevent I/R injury than targeting the intracellular pathways used by TLR4. In conclusion, we identified TLR4 as a cellular sentinel for acute renal damage that subsequently controls the induction of an innate immune response.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-10201887,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-10487768,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-10962277,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-11143986,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-11469899,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-11477402,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-11801667,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-12467243,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-12471095,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-12750407,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-12855817,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-12872135,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-12906258,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-1431091,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-14556004,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-14751757,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-14764737,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-15178705,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-15229469,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-15585830,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-15765149,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-15829714,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-15863899,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-15912106,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-16007092,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-16167081,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-16319494,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-16603631,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-16609927,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-16720897,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-16753195,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-16782386,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-16822173,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-16843693,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-16952555,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-17126102,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-17238832,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-17257219,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-17439747,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-17475853,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18974879-9697844
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:issn |
1932-6203
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
3
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
e3596
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:18974879-Adaptor Proteins, Vesicular Transport,
pubmed-meshheading:18974879-Animals,
pubmed-meshheading:18974879-Apoptosis,
pubmed-meshheading:18974879-Cell Proliferation,
pubmed-meshheading:18974879-Genetic Predisposition to Disease,
pubmed-meshheading:18974879-Granulocytes,
pubmed-meshheading:18974879-Immunity, Innate,
pubmed-meshheading:18974879-Inflammation,
pubmed-meshheading:18974879-Kidney,
pubmed-meshheading:18974879-Kidney Diseases,
pubmed-meshheading:18974879-Mice,
pubmed-meshheading:18974879-Mice, Knockout,
pubmed-meshheading:18974879-Myeloid Differentiation Factor 88,
pubmed-meshheading:18974879-Neutrophil Infiltration,
pubmed-meshheading:18974879-Reperfusion Injury,
pubmed-meshheading:18974879-Toll-Like Receptor 4
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pubmed:year |
2008
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pubmed:articleTitle |
Toll-like receptor-4 coordinates the innate immune response of the kidney to renal ischemia/reperfusion injury.
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pubmed:affiliation |
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. w.p.pulskens@amc.uva.nl
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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