Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2010-5-4
pubmed:abstractText
BACKGROUND.: A neutrophil elastase (NE) inhibitor, Sivelestat, has been approved for the treatment of acute lung injury associated with systemic inflammation in humans. Some reports have also shown its protective effects in liver inflammatory states. We have recently documented the importance of NE in the pathophysiology of liver ischemia/reperfusion injury, a local Ag-independent inflammation response. This study was designed to explore putative cytoprotective functions of clinically available Sivelestat in liver ischemia/reperfusion injury. METHODS.: Partial warm ischemia was produced in the left and middle hepatic lobes of C57BL/6 mice for 90 min, followed by 6 or 24 hr of reperfusion. The mice were given Sivelestat (100 mg/kg, subcutaneous) at 10 min before ischemia, 10 min before reperfusion, and at 1 and 3 hr of reperfusion thereafter. RESULTS.: Sivelestat treatment significantly reduced serum alanine aminotransferase levels and NE activity, when compared with controls. Histological liver examination has revealed that unlike in controls, Sivelestat ameliorated the hepatocellular damage and decreased local neutrophil activity and infiltration. The expression of proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), chemokines (CXCL-1, CXCL-2, and CXCL-10), and toll-like receptor 4 was significantly reduced in the treatment group, along with diminished apoptosis through caspase-3 pathway. Moreover, in vitro studies confirmed downregulation of proinflammatory cytokine and chemokine programs in mouse macrophage cell cultures, along with depression of innate toll-like receptor 4 signaling. CONCLUSION.: Sivelestat-mediated NE inhibition may represent an effective therapeutic option in liver transplantation and other inflammation disease states.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL1, http://linkedlifedata.com/resource/pubmed/chemical/Cxcl1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers, http://linkedlifedata.com/resource/pubmed/chemical/Glycine, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6, http://linkedlifedata.com/resource/pubmed/chemical/Leukocyte Elastase, http://linkedlifedata.com/resource/pubmed/chemical/ONO 5046, http://linkedlifedata.com/resource/pubmed/chemical/Peroxidase, http://linkedlifedata.com/resource/pubmed/chemical/Proteinase Inhibitory Proteins..., http://linkedlifedata.com/resource/pubmed/chemical/RNA, http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1534-6080
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1050-6
pubmed:dateRevised
2011-1-14
pubmed:meshHeading
pubmed-meshheading:20160675-Animals, pubmed-meshheading:20160675-Chemokine CXCL1, pubmed-meshheading:20160675-DNA Primers, pubmed-meshheading:20160675-Glycine, pubmed-meshheading:20160675-Humans, pubmed-meshheading:20160675-Immunohistochemistry, pubmed-meshheading:20160675-Inflammation, pubmed-meshheading:20160675-Interleukin-6, pubmed-meshheading:20160675-Leukocyte Elastase, pubmed-meshheading:20160675-Liver, pubmed-meshheading:20160675-Male, pubmed-meshheading:20160675-Mice, pubmed-meshheading:20160675-Mice, Inbred C57BL, pubmed-meshheading:20160675-Neutrophils, pubmed-meshheading:20160675-Peroxidase, pubmed-meshheading:20160675-Polymerase Chain Reaction, pubmed-meshheading:20160675-Proteinase Inhibitory Proteins, Secretory, pubmed-meshheading:20160675-RNA, pubmed-meshheading:20160675-Reperfusion Injury, pubmed-meshheading:20160675-Sulfonamides, pubmed-meshheading:20160675-Tumor Necrosis Factor-alpha
pubmed:year
2010
pubmed:articleTitle
The protective function of neutrophil elastase inhibitor in liver ischemia/reperfusion injury.
pubmed:affiliation
Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural