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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
1992-12-8
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pubmed:abstractText |
We have previously established that IFN-gamma plus IL-2 induces murine macrophage tumoricidal activity. The purpose of this study was to identify the effector molecules that account for the IFN-gamma plus IL-2-induced macrophage cytotoxicity against P815 mastocytoma cells. ANA-1 macrophages and normal thioglycollate-elicited mouse peritoneal macrophages produced little or no detectable nitrite (NO2-) after incubation with IFN-gamma alone or IL-2 alone; however, IL-2 synergized with IFN-gamma for the production of NO2-. IFN-gamma plus IL-2 did not induce NO2- production or tumoricidal activity in ANA-1 macrophages that were cultured in medium devoid of L-arginine or in ANA-1 macrophages that were incubated with NG-monomethyl-L-arginine. As observed previously with ANA-1 macrophage tumoricidal activity, IL-4 inhibited IFN-gamma plus IL-2-induced, but not IFN-gamma plus LPS-induced, NO2- production. IL-4 also selectively decreased the ability of IFN-gamma and/or IL-2 to augment TNF-alpha mRNA expression in ANA-1 macrophages. Lastly, incubation of ANA-1 macrophages with anti-TNF mAb selectively inhibited the ability of IFN-gamma plus IL-2 to induce NO2- production and tumoricidal activity. These results indicate that IFN-gamma plus IL-2-induced tumoricidal activity is dependent upon the metabolism of L-arginine to reactive nitrogen intermediates, and they establish a role for TNF-alpha as a required intermediate for IL-2-dependent NO2- production and tumoricidal activity.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
149
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3290-6
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:1431106-Animals,
pubmed-meshheading:1431106-Arginine,
pubmed-meshheading:1431106-Cells, Cultured,
pubmed-meshheading:1431106-Cytotoxicity, Immunologic,
pubmed-meshheading:1431106-Interferon-gamma,
pubmed-meshheading:1431106-Interleukin-2,
pubmed-meshheading:1431106-Interleukin-4,
pubmed-meshheading:1431106-Lipopolysaccharides,
pubmed-meshheading:1431106-Macrophages,
pubmed-meshheading:1431106-Mast-Cell Sarcoma,
pubmed-meshheading:1431106-Mice,
pubmed-meshheading:1431106-Nitric Oxide,
pubmed-meshheading:1431106-RNA, Messenger,
pubmed-meshheading:1431106-Tumor Necrosis Factor-alpha
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pubmed:year |
1992
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pubmed:articleTitle |
Tumor necrosis factor-alpha-dependent production of reactive nitrogen intermediates mediates IFN-gamma plus IL-2-induced murine macrophage tumoricidal activity.
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pubmed:affiliation |
Laboratory of Molecular Immunoregulation, National Cancer Institute-Frederick Cancer Research and Development Center, National Institutes of Health, MD 21702-1201.
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pubmed:publicationType |
Journal Article
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