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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
1998-10-2
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pubmed:abstractText |
1. The role of the L-arginine-nitric oxide (NO) pathway on the formation of prostaglandin E2 (PGE2) by human cultured astroglial cells incubated with interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) was investigated. 2. Incubation of T 67 astroglial cell line with IL-beta (10 ng ml(-1)) and TNF-alpha (500 u ml(-1)) produced a significant (P<0.05) increase of both nitrite (the breakdown product of NO), cyclic GMP and PGE2 levels in cell supernatants. N omega-nitro-L-arginine methyl ester (L-NAME; 20-300 microM), an inhibitor of NO synthase (NOS), inhibited the increase of cyclic GMP and nitrite levels found in supernatants of cytokine-treated astroglial cells and reduced the release of PGE2. The latter effect showed that the enhanced arachidonic acid (AA) metabolism subsequent to stimulation of astroglial cells with IL-1beta and TNF-alpha was, at least in part, induced by NO. This occurred also when sodium nitroprusside (SNP; 120 microM), an NO donor, was incubated with astroglial cells, an effect antagonized by oxyhaemoglobin (OxyHb; 10 microM). 3. The inhibition elicited by L-NAME on PGE2-release by cytokine-treated astroglial cells was reversed by adding AA (40 microM), showing that the effect of NO on cytokine-dependent PGE2 release occurred at the cyclo-oxygenase (COX) level. Furthermore, the release of PGE2 in cytokine-treated astroglial cells was inhibited by indomethacin (10 microM), a COX inhibitor as well as by preincubating cells with dexamethasone (20 microM), an inhibitor of inducible enzymes, showing that the inducible isoform of COX (COX-2) was involved. 4. On the other hand, pretreating astroglial cells with methylene blue (MB; 10 microM), an inhibitor of NO biological activity acting at the guanylate cyclase level, failed to affect PGE2 release in cytokine-treated astroglial cells, leading to the conclusion that cyclic GMP changes related to NO formation are not involved in the generation of AA metabolites. 5. The present experiments demonstrated that the release of PGE2 by astroglial cells pretreated with IL-1beta and TNF-alpha is due to enhanced COX-2 activity via activation of the L-arginine-NO pathway, and this may be relevant to the understanding of the pathophysiological mechanisms underlying neuroimmune disorders.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2 Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NG-Nitroarginine Methyl Ester,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrites,
http://linkedlifedata.com/resource/pubmed/chemical/Nitroprusside,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0007-1188
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
124
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
742-6
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pubmed:dateRevised |
2008-11-20
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pubmed:meshHeading |
pubmed-meshheading:9690866-Astrocytes,
pubmed-meshheading:9690866-Cell Line,
pubmed-meshheading:9690866-Cyclic GMP,
pubmed-meshheading:9690866-Cyclooxygenase 2,
pubmed-meshheading:9690866-Cyclooxygenase 2 Inhibitors,
pubmed-meshheading:9690866-Cyclooxygenase Inhibitors,
pubmed-meshheading:9690866-Dexamethasone,
pubmed-meshheading:9690866-Dinoprostone,
pubmed-meshheading:9690866-Enzyme Induction,
pubmed-meshheading:9690866-Enzyme Inhibitors,
pubmed-meshheading:9690866-Humans,
pubmed-meshheading:9690866-Interleukin-1,
pubmed-meshheading:9690866-Isoenzymes,
pubmed-meshheading:9690866-Membrane Proteins,
pubmed-meshheading:9690866-NG-Nitroarginine Methyl Ester,
pubmed-meshheading:9690866-Nitric Oxide,
pubmed-meshheading:9690866-Nitric Oxide Synthase,
pubmed-meshheading:9690866-Nitrites,
pubmed-meshheading:9690866-Nitroprusside,
pubmed-meshheading:9690866-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:9690866-Tumor Necrosis Factor-alpha
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pubmed:year |
1998
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pubmed:articleTitle |
The effect of nitric oxide on cytokine-induced release of PGE2 by human cultured astroglial cells.
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pubmed:affiliation |
Department of Biology, University of Rome Tor Vergata, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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