Linked Life Data

11699074

Source:http://linkedlifedata.com/resource/pubmed/id/11699074

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2001-11-8
pubmed:abstractText
Through their effects on gene activation, antioxidants have been reported to modulate cellular expression of several proinflammatory cytokines and adhesion molecules, an effect mediated by preventing translocation of the transcription factor nuclear factor-kappa B (NF-kappa B) into the nucleus. In addition, modulation of the intracellular redox state may have profound effects on cell activation and subsequent gene expression distinct from effects on NF-kappa B; these effects may account for the divergent effects of antioxidants on cytokine gene expression in various reports. In the present studies, we evaluated the effect of the antioxidant, pyrrolidine dithiocarbamate (PDTC), on murine and human myeloid cell tumor necrosis factor alpha (TNF alpha) gene and protein expression. PDTC-enhanced LPS-induced TNF alpha secretion in cells derived from a murine macrophage cell line (J774.1), as well as in primary murine peritoneal macrophages by 4-fold. The effect was both stimulus and species dependent, as TNF alpha secretion was attenuated by PDTC in human THP-1 cells and in murine cells stimulated with zymosan. Northern analysis demonstrated that these effects were evident at the level of mRNA expression. Electrophoretic mobility shift assays confirmed the down-regulatory effect of PDTC on human myeloid NF-kappa B activation, whereas in murine cells no such inhibitory effect was evident. Evaluation of TNF alpha mRNA stability in murine cells demonstrated that the potentiating effect of PDTC on TNF alpha mRNA expression was due to an increase in mRNA half-life from 37 to 93 min. Together, these data suggest that the effect of antioxidants on gene expression are both stimulus and species dependent and illustrate a novel mechanism whereby redox manipulation might modulate TNF alpha expression in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1073-2322
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
361-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Antioxidants increase lipopolysaccharide-stimulated TNF alpha release in murine macrophages: role for altered TNF alpha mRNA stability.
pubmed:affiliation
Department of Surgery, University of Washington, Seattle, Washington, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't