|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
5
|
|
pubmed:dateCreated |
2001-3-6
|
|
pubmed:abstractText |
The proinflammatory cytokine IL-18 was investigated for its role in human myocardial function. An ischemia/reperfusion (I/R) model of suprafused human atrial myocardium was used to assess myocardial contractile force. Addition of IL-18 binding protein (IL-18BP), the constitutive inhibitor of IL-18 activity, to the perifusate during and after I/R resulted in improved contractile function after I/R from 35% of control to 76% with IL-18BP. IL-18BP treatment also preserved intracellular tissue creatine kinase levels (by 420%). Steady-state mRNA levels for IL-18 were elevated after I/R, and the concentration of IL-18 in myocardial homogenates was increased (control, 5.8 pg/mg vs. I/R, 26 pg/mg; P < 0.01). Active IL-18 requires cleavage of its precursor form by the IL-1beta-converting enzyme (caspase 1); inhibition of caspase 1 also attenuated the depression in contractile force after I/R (from 35% of control to 75.8% in treated atrial muscle; P < 0.01). Because caspase 1 also cleaves the precursor IL-1beta, IL-1 receptor blockade was accomplished by using the IL-1 receptor antagonist. IL-1 receptor antagonist added to the perifusate also resulted in a reduction of ischemia-induced contractile dysfunction. These studies demonstrate that endogenous IL-18 and IL-1beta play a significant role in I/R-induced human myocardial injury and that inhibition of caspase 1 reduces the processing of endogenous precursors of IL-18 and IL-1beta and thereby prevents ischemia-induced myocardial dysfunction.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-10023777,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-10051628,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-10210635,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-10446825,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-10471354,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-10655506,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-10681439,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-10690285,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-10728385,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-1631560,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-2203553,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-3826401,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-7536096,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-7558306,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-7856752,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-7943392,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-8331924,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-8628393,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-8642298,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-8752821,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-8999548,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-9054727,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-9121587,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-9236412,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-9325300,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-9354477,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-9485242,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-9545547,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-9698510,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-9792649,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11226333-9893178
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Creatine Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/IL1RN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin 1 Receptor Antagonist...,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-18,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Sialoglycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/interleukin-18 binding protein
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Feb
|
|
pubmed:issn |
0027-8424
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
27
|
|
pubmed:volume |
98
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
2871-6
|
|
pubmed:dateRevised |
2009-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:11226333-Animals,
pubmed-meshheading:11226333-CHO Cells,
pubmed-meshheading:11226333-Caspase 1,
pubmed-meshheading:11226333-Creatine Kinase,
pubmed-meshheading:11226333-Cricetinae,
pubmed-meshheading:11226333-Glycoproteins,
pubmed-meshheading:11226333-Humans,
pubmed-meshheading:11226333-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:11226333-Interleukin 1 Receptor Antagonist Protein,
pubmed-meshheading:11226333-Interleukin-1,
pubmed-meshheading:11226333-Interleukin-18,
pubmed-meshheading:11226333-Microscopy, Confocal,
pubmed-meshheading:11226333-Myocardial Ischemia,
pubmed-meshheading:11226333-Myocardium,
pubmed-meshheading:11226333-RNA, Messenger,
pubmed-meshheading:11226333-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:11226333-Sialoglycoproteins
|
|
pubmed:year |
2001
|
|
pubmed:articleTitle |
Inhibition of caspase 1 reduces human myocardial ischemic dysfunction via inhibition of IL-18 and IL-1beta.
|
|
pubmed:affiliation |
Department of Surgery, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|
