Linked Life Data

21567435

Source:http://linkedlifedata.com/resource/pubmed/id/21567435

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-7-27
pubmed:abstractText
Pre-B cell colony-enhancing factor (PBEF), also known as nicotinamide phosphoribosyltransferase or visfatin, plays an important role in metabolic, inflammatory, and malignant diseases. Recent evidence suggests that blocking its enzymatic activity using a specific small-molecule inhibitor (FK866) might be beneficial in acute experimental inflammation. We investigated the role of PBEF in human liver disease and experimental hepatitis. PBEF serum levels and hepatic expression were determined in patients with chronic liver diseases. These studies were followed by in vivo experiments using concanavalin A (ConA) and D-galactosamine/lipopolysaccharide (LPS) models of experimental hepatitis. PBEF was either overexpressed by hydrodynamic perfusion or inhibited by FK866. In vivo findings were corroborated studying inflammatory responses of lentivirally PBEF-silenced or control FL83B mouse hepatocytes. Here, we demonstrate that PBEF serum levels were increased in patients with chronic liver diseases irrespective of disease stage and etiology. In particular, we observed enhanced PBEF expression in hepatocytes. Liver-targeted overexpression of PBEF rendered mice more susceptible to ConA- and D-galactosamine/LPS-induced hepatitis compared with control animals. In contrast, inhibition of PBEF using FK866 protected mice from ConA-induced liver damage and apoptosis. Administration of FK866 resulted in depletion of liver nicotinamide adenine dinucleotide+ levels and reduced proinflammatory cytokine expression. Additionally, FK866 protected mice in the D-galactosamine/LPS model of acute hepatitis. In vitro, PBEF-silenced mouse hepatocytes showed decreased responses after stimulation with LPS, lipoteichoic acid, and tumor necrosis factor ?. In primary murine Kupffer cells, FK866 suppressed LPS-induced interleukin (IL)-6 production, whereas incubation with recombinant PBEF resulted in increased IL-6 release. CONCLUSION: Our data suggest that PBEF is of key importance in experimental hepatitis. Its specific inhibition might be considered a novel treatment option for inflammatory liver diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1527-3350
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 American Association for the Study of Liver Diseases.
pubmed:issnType
Electronic
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
675-86
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
A key role for Pre-B cell colony-enhancing factor in experimental hepatitis.
pubmed:affiliation
Christian Doppler Research Laboratory for Gut Inflammation, Department of Internal Medicine II, Gastroenterology & Hepatology, Medical University Innsbruck, Innsbruck, Austria.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't