Source:http://linkedlifedata.com/resource/pubmed/id/21511702
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2011-7-7
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| pubmed:abstractText |
Renal tubular cell apoptosis is a significant component of obstruction-induced renal injury, and it results in a progressive loss in renal parenchymal mass during renal obstruction. Although IL-18 is an important mediator of inflammatory renal disease and renal fibrosis, its role in obstruction-induced renal tubular cell apoptosis remains unclear. To study this, male C57BL6 wild-type mice and C57BL6 mice transgenic for human IL-18-binding protein (IL-18BP Tg) were subjected to renal obstruction vs. sham operation. The kidneys were harvested after 1 or 2 wk and analyzed for IL-18 production, apoptosis, caspase activity, and Fas/Fas Ligand (FasL) expression. HK-2 cells were similarly analyzed for apoptosis and proapoptotic signaling following 3 days of direct exposure to IL-18 vs. control media. Renal obstruction induced a significant increase in IL-18 production, renal tubular cell apoptosis, caspase activation, and FasL expression. IL-18 neutralization, on the other hand, significantly reduced obstruction-induced apoptosis, caspase-8 and caspase-3 activity, and FasL expression. In vitro experiments similarly demonstrate that IL-18 stimulation induces apoptosis, FasL expression, and increases active caspase-8 and caspase-3 expression in a dose-dependent fashion. siRNA knockdown of FasL gene expression, however, significantly reduced IL-18-induced apoptosis. This study reveals that IL-18 is a significant mediator of obstruction-induced tubular cell apoptosis, and it demonstrates that IL-18 stimulates proapoptotic signaling through a FasL-dependent mechanism.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Fas Ligand Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-18,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/interleukin-18 binding protein
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
1522-1466
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
301
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
F171-8
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| pubmed:meshHeading |
pubmed-meshheading:21511702-Animals,
pubmed-meshheading:21511702-Apoptosis,
pubmed-meshheading:21511702-Blotting, Western,
pubmed-meshheading:21511702-Caspases,
pubmed-meshheading:21511702-Cells, Cultured,
pubmed-meshheading:21511702-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:21511702-Fas Ligand Protein,
pubmed-meshheading:21511702-Flow Cytometry,
pubmed-meshheading:21511702-Humans,
pubmed-meshheading:21511702-In Situ Nick-End Labeling,
pubmed-meshheading:21511702-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:21511702-Interleukin-18,
pubmed-meshheading:21511702-Kidney Tubules, Proximal,
pubmed-meshheading:21511702-Male,
pubmed-meshheading:21511702-Mice,
pubmed-meshheading:21511702-Mice, Inbred C57BL,
pubmed-meshheading:21511702-Mice, Transgenic,
pubmed-meshheading:21511702-RNA, Small Interfering,
pubmed-meshheading:21511702-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:21511702-Signal Transduction,
pubmed-meshheading:21511702-Transfection,
pubmed-meshheading:21511702-Ureteral Obstruction
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| pubmed:year |
2011
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| pubmed:articleTitle |
IL-18 mediates proapoptotic signaling in renal tubular cells through a Fas ligand-dependent mechanism.
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| pubmed:affiliation |
Department of Urology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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