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rdf:type |
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lifeskim:mentions |
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0026809,
umls-concept:C0035078,
umls-concept:C0037083,
umls-concept:C0079904,
umls-concept:C0389995,
umls-concept:C0599946,
umls-concept:C1335631,
umls-concept:C1420556,
umls-concept:C1424530,
umls-concept:C1710082
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pubmed:issue |
5
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pubmed:dateCreated |
2009-4-27
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pubmed:abstractText |
Rho kinase signaling regulates inflammatory cell migration and chemokine production. We therefore investigated the mechanisms of Rho-kinase-dependent inflammation in lipopolysaccharide (LPS)-induced renal failure. C57/BL6 mice received intraperitoneal LPS with or without daily treatment with specific Rho kinase inhibitors (Y-27632 or HA-1077; 5 mg/kg). Rho kinase inhibitors were applied in a preventive (12 or 1 h before LPS) or a therapeutic (6 h after LPS) scheme. Both protected renal function and decreased tubular injury in LPS-treated mice. Enhanced Rho kinase activity was inhibited by HA-1077 in capillary endothelial cells, inflammatory cells, and tubuli by analysis of Rho kinase substrate phosphorylation. Early neutrophil influx was reduced by HA-1077 without reduction of the proinflammatory cytokine TNFalpha. In contrast, HA-1077 decreased the influx of monocytes/macrophages coinciding with reduced expression of the NF-kappaB-regulated chemokines CCL5 and CCL2. We therefore examined NF-kappaB signal transduction and found that NF-kappaB p65 phosphorylation and nuclear translocation were reduced by Rho kinase inhibition. IkappaBalpha degradation was not altered during the first 6 h but was reduced by HA-1077 at later time points. NF-kappaB p50-deficient mice were similarly protected from renal injury by Rho kinase inhibition further supporting the prominent role for p65 in Rho kinase inhibition. Together, these data suggest that Rho kinase inhibition by preventive or therapeutic treatment effectively reduced endotoxic kidney injury in part by attenuation of NF-kappaB p65 activation.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/1-(5-Isoquinolinesulfonyl)-2-Methylp...,
http://linkedlifedata.com/resource/pubmed/chemical/Amides,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B p50 Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor RelA,
http://linkedlifedata.com/resource/pubmed/chemical/Y 27632,
http://linkedlifedata.com/resource/pubmed/chemical/fasudil,
http://linkedlifedata.com/resource/pubmed/chemical/rho-Associated Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1931-857X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
296
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
F1088-99
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pubmed:dateRevised |
2011-4-28
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pubmed:meshHeading |
pubmed-meshheading:19225047-1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine,
pubmed-meshheading:19225047-Amides,
pubmed-meshheading:19225047-Animals,
pubmed-meshheading:19225047-Cell Nucleus,
pubmed-meshheading:19225047-Chemokines,
pubmed-meshheading:19225047-Enzyme Inhibitors,
pubmed-meshheading:19225047-Female,
pubmed-meshheading:19225047-Kidney,
pubmed-meshheading:19225047-Leukocytes,
pubmed-meshheading:19225047-Lipopolysaccharides,
pubmed-meshheading:19225047-Male,
pubmed-meshheading:19225047-Mice,
pubmed-meshheading:19225047-Mice, Inbred C57BL,
pubmed-meshheading:19225047-Mice, Mutant Strains,
pubmed-meshheading:19225047-NF-kappa B p50 Subunit,
pubmed-meshheading:19225047-Nephritis,
pubmed-meshheading:19225047-Phosphorylation,
pubmed-meshheading:19225047-Protein Kinase Inhibitors,
pubmed-meshheading:19225047-Pyridines,
pubmed-meshheading:19225047-Renal Insufficiency,
pubmed-meshheading:19225047-Signal Transduction,
pubmed-meshheading:19225047-Transcription Factor RelA,
pubmed-meshheading:19225047-rho-Associated Kinases
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pubmed:year |
2009
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pubmed:articleTitle |
Rho kinase inhibition attenuates LPS-induced renal failure in mice in part by attenuation of NF-kappaB p65 signaling.
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pubmed:affiliation |
Department of Internal Medicine, University Hospital Hamburg, Hamburg, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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