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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2002-9-2
pubmed:abstractText
Tumor necrosis factor a (TNF-alpha) is a pleiotropic cytokine involved in several diseases. Various effects of TNF-alpha are mediated by the induction of a cellular state consistent with oxidative stress. Glutathione (GSH) is a major redox-buffer of eukaryotic cells and is important in the defense against oxidative stress. We hypothesized that persistent TNF-alpha secretion could induce oxidative stress through modulation of GSH metabolism. This hypothesis was examined in a transgenic mouse model with low, persistent expression of human TNF-alpha in the T cell compartment. Major findings were i) marked tissue-specific changes in GSH redox status and GSH regulating enzymes, with the most pronounced changes in liver; ii) moderate changes in GSH metabolism and up-regulation of GSH-regulating enzymes were observed in lung and kidney from transgenic mice; and iii) liver, lung and kidney from transgenic mice had decreased levels of total glutathione, whereas splenic CD4+ and CD8+ T cells had a marked increase in oxidized glutathione as the major change. Oxidative stress induced by persistent low-grade exposure to TNF-alpha in transgenic mice appears to involve marked organ-specific alterations in glutathione redox status and glutathione-regulating enzymes with the most pronounced changes in the liver. These mice constitute a useful model for immunodeficiency syndromes and chronic inflammatory diseases involving pathogenic interaction between TNF-alpha and oxidative stress.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1450-2
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Human TNF-alpha in transgenic mice induces differential changes in redox status and glutathione-regulating enzymes.
pubmed:affiliation
Biotechnology Centre of Oslo, University of Oslo, PB 1125 Blindern, 0317 Oslo, Norway.
pubmed:publicationType
Journal Article