Source:http://linkedlifedata.com/resource/pubmed/id/19536084
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2009-8-14
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pubmed:abstractText |
Ureteral obstruction results in renal fibrosis in part due to inflammatory injury. The role of interleukin-18 (IL-18), an important mediator of inflammation, in the genesis of renal fibrosis was studied using transgenic mice overexpressing human IL-18-binding protein. In addition, HK-2 cells were analyzed following direct exposure to IL-18 compared to control media. Two weeks after ureteral obstruction, the kidneys of wild-type mice had a significant increase in IL-18 production, collagen deposition, alpha-smooth muscle actin and RhoA expression, fibroblast and macrophage accumulation, chemokine expression, and transforming growth factor-beta1 (TGF-beta1) and tumor necrosis factor-alpha (TNF-alpha) production, whereas E-cadherin expression was simultaneously decreased. The transgenic mice with neutralized IL-18 activity exhibited significant reductions in these indicators of obstruction-induced renal fibrosis and epithelial- mesenchymal transition, without demonstrating alterations in TGF-beta1 or TNF-alpha activity. Similarly, the HK-2 cells exhibited increased alpha-smooth muscle actin expression and collagen production, and decreased E-cadherin expression in response to IL-18 stimulation without alterations in TNF-alpha or TGF-beta1 activity. Our study demonstrates that IL-18 is a significant mediator of obstruction-induced renal fibrosis and epithelial- mesenchymal transition independent of downstream TGF-beta1 or TNF-alpha production.
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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/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-18,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-smooth muscle actin, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/interleukin-18 binding protein
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1523-1755
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
76
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
500-11
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pubmed:dateRevised |
2011-1-13
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pubmed:meshHeading |
pubmed-meshheading:19536084-Actins,
pubmed-meshheading:19536084-Animals,
pubmed-meshheading:19536084-Cell Line,
pubmed-meshheading:19536084-Chemokines,
pubmed-meshheading:19536084-Collagen,
pubmed-meshheading:19536084-Epithelial Cells,
pubmed-meshheading:19536084-Fibrosis,
pubmed-meshheading:19536084-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:19536084-Interleukin-18,
pubmed-meshheading:19536084-Kidney,
pubmed-meshheading:19536084-Macrophages,
pubmed-meshheading:19536084-Male,
pubmed-meshheading:19536084-Mesoderm,
pubmed-meshheading:19536084-Mice,
pubmed-meshheading:19536084-Mice, Inbred C57BL,
pubmed-meshheading:19536084-RNA, Messenger,
pubmed-meshheading:19536084-Transforming Growth Factor beta1,
pubmed-meshheading:19536084-Tumor Necrosis Factor-alpha
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pubmed:year |
2009
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pubmed:articleTitle |
IL-18 neutralization ameliorates obstruction-induced epithelial-mesenchymal transition and renal fibrosis.
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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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