Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2000-11-27
pubmed:abstractText
Expression of inducible nitric oxide synthase (iNOS) protein was studied in the brain after intracerebroventricular injections of interferon (IFN)-gamma, and IFN-gamma combined with lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-alpha, compared to ovalbumin as control. Wild-type mice and mice with targeted deletion of the IFN-gamma receptor gene were used. Findings based on iNOS immunoreactivity were evaluated at 1, 2, 4 and 7 days post-injection, using also quantitative image analysis and double labeling with glial cell markers. IFN-gamma administration induced iNOS immmunostaining in activated microglia and macrophages in the parenchyma surrounding the ventricular system, several cortical fields and fiber tracts. IFN-gamma-elicited iNOS immunoreactivity was down-regulated after 1 day. The number of iNOS-immunopositive cells was significantly enhanced by co-administration of LPS or TNF-alpha; IFN-gamma+TNF-alpha injections also resulted in longer persistence of iNOS immunoreactivity. No immunopositive cells were seen in the brain of IFN-gamma receptor knockout mice after IFN-gamma administration; very few immunostained macrophages were detected in these cases, mostly around the injection needle track, after co-administration of LPS or TNF-alpha. Western blot analysis confirmed a marked iNOS induction in the brain of wild-type mice 24 h after IFN-gamma+LPS injections. The findings show that inflammatory mediators circulating in the cerebrospinal fluid induce in vivo iNOS in the brain with topographical selectivity and temporal regulation. The data also demonstrate that the signaling cascade activated by IFN-gamma binding to its receptor is critical for iNOS induction, and the synergistic action of LPS and TNF-alpha as iNOS inducers in brain cells is largely mediated by the receptor-regulated action of IFN-gamma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
878
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
105-18
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10996141-Animals, pubmed-meshheading:10996141-Blotting, Western, pubmed-meshheading:10996141-Brain, pubmed-meshheading:10996141-Immunohistochemistry, pubmed-meshheading:10996141-Inflammation Mediators, pubmed-meshheading:10996141-Injections, Intraventricular, pubmed-meshheading:10996141-Interferon-gamma, pubmed-meshheading:10996141-Lipopolysaccharides, pubmed-meshheading:10996141-Mice, pubmed-meshheading:10996141-Mice, Inbred C57BL, pubmed-meshheading:10996141-Mice, Knockout, pubmed-meshheading:10996141-Nitric Oxide Synthase, pubmed-meshheading:10996141-Nitric Oxide Synthase Type II, pubmed-meshheading:10996141-Receptors, Interferon, pubmed-meshheading:10996141-Reference Values, pubmed-meshheading:10996141-Time Factors, pubmed-meshheading:10996141-Tissue Distribution, pubmed-meshheading:10996141-Tumor Necrosis Factor-alpha
pubmed:year
2000
pubmed:articleTitle
Inducible nitric oxide synthase expression elicited in the mouse brain by inflammatory mediators circulating in the cerebrospinal fluid.
pubmed:affiliation
Department of Morphological and Biomedical Sciences, University of Verona, Verona, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't