Linked Life Data

9500699

Source:http://linkedlifedata.com/resource/pubmed/id/9500699

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-3-19
pubmed:abstractText
The multiple interlocking regulatory mechanisms that underlie induction of hepatocyte inducible nitric oxide synthase (iNOS) expression are largely unknown. Although previous work has indicated the requirement for multiple proinflammatory cytokines to induce hepatocyte NO production, investigators have recently shown that interleukin-1beta (IL-1beta) alone can initiate iNOS expression. In contrast, interferon gamma (IFN-gamma) serves as the sole initiating factor in other cell systems. On the basis of the known ability of IL-1beta to induce transcription and translation of the IFN family of genes, we hypothesized that IL-1beta-mediated hepatocyte expression of iNOS is dependent on endogenous IFN-gamma synthesis. In a system of rat hepatocytes in primary culture, IL-1beta induced production of both NO and IFN-gamma. Using in situ hybridization and immunoblot analysis, IFN-gamma messenger RNA (mRNA) and protein were detected in hepatocytes exposed to IL-1beta. Inhibition of NO synthesis using the competitive substrate inhibitor N-monomethyl-L-arginine (100 micromol/L) did not alter the extent of IL-1beta-mediated IFN-gamma synthesis. In contrast, anti-IFN-gamma antibody or inhibition of IFN-gamma mRNA translation by addition of antisense IFN-gamma oligodeoxynucleotide probes resulted in undetectable levels of NO metabolites and iNOS protein. Repletion of IFN-gamma to the system restored NO production to levels noted in the presence of IL-1beta alone. Transient transfection analysis using a rat hepatocyte iNOS promoter-reporter gene plasmid construct showed that IL-1beta-induced promoter activation was abolished in the presence of anti-IFN-gamma or antisense IFN-gamma. Again, addition of IFN-gamma to the system restored activity of the iNOS promoter. Parallel experiments examining IL-1beta-mediated endogenous hepatocyte IL-1beta and TNF-alpha synthesis indicated no role for these cytokines in the induction of iNOS expression by IL-1beta. It is concluded that IL-1beta-mediated hepatocyte synthesis of NO is dependent on the simultaneous endogenous synthesis of IFN-gamma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
711-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Interleukin 1beta-stimulated production of nitric oxide in rat hepatocytes is mediated through endogenous synthesis of interferon gamma.
pubmed:affiliation
Department of Surgery, University of Maryland Medical System, Baltimore 21201, USA.
pubmed:publicationType
Journal Article