Source:http://linkedlifedata.com/resource/pubmed/id/12193733
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2002-8-23
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| pubmed:abstractText |
NO appears as an important determinant in auto and paracrine macrophage function. We hypothesized that NO switches monocyte/macrophage function from a pro- to an anti-inflammatory phenotype by activating anti-inflammatory properties of the peroxisome proliferator-activated receptor (PPAR)gamma. NO-releasing compounds (100 micro M S-nitrosoglutathione or 50 micro M spermine-NONOate) as well as inducible NO synthase induction provoked activation of PPARgamma. This was proven by EMSAs, with the notion that supershift analysis pointed to the involvement of PPARgamma. PCR analysis ruled out induction of PPARgamma mRNA as a result of NO supplementation. Reporter assays, with a construct containing a triple PPAR response element in front of a thymidine kinase minimal promoter driving the luciferase gene, were positive in response to NO delivery. DNA binding capacity as well as the transactivating capability of PPARgamma were attenuated by addition of the antioxidant N-acetyl-cysteine or in the presence of the NO scavenger 2-phenyl-4,4,5,6-tetramethyl-imidazoline-1-oxyl 3-oxide. Having established that NO but not lipophilic cyclic GMP analogs activated PPARgamma, we verified potential anti-inflammatory consequences. The oxidative burst of macrophages, evoked by phorbol ester, was attenuated in association with NO-elicited PPARgamma activation. A cause-effect relationship was demonstrated when PPAR response element decoy oligonucleotides, supplied in front of NO delivery, allowed to regain an oxidative response. PPARgamma-mediated down-regulation of p47 phagocyte oxidase, a component of the NAD(P)H oxidase system, was identified as one molecular mechanism causing inhibition of superoxide radical formation. We conclude that NO participates in controlling the pro- vs anti-inflammatory phenotype of macrophages by modulating PPARgamma.
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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/Free Radicals,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/NOS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Donors,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Nos2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/S-Nitrosoglutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxides,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/neutrophil cytosolic factor 1
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
1
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| pubmed:volume |
169
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2619-26
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| pubmed:dateRevised |
2011-10-27
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| pubmed:meshHeading |
pubmed-meshheading:12193733-Animals,
pubmed-meshheading:12193733-Cell Line,
pubmed-meshheading:12193733-Down-Regulation,
pubmed-meshheading:12193733-Enzyme Induction,
pubmed-meshheading:12193733-Free Radicals,
pubmed-meshheading:12193733-Humans,
pubmed-meshheading:12193733-Macrophages,
pubmed-meshheading:12193733-Mice,
pubmed-meshheading:12193733-Monocytes,
pubmed-meshheading:12193733-NADPH Oxidase,
pubmed-meshheading:12193733-Nitric Oxide,
pubmed-meshheading:12193733-Nitric Oxide Donors,
pubmed-meshheading:12193733-Nitric Oxide Synthase,
pubmed-meshheading:12193733-Nitric Oxide Synthase Type II,
pubmed-meshheading:12193733-Peroxisomes,
pubmed-meshheading:12193733-Phosphoproteins,
pubmed-meshheading:12193733-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:12193733-Respiratory Burst,
pubmed-meshheading:12193733-S-Nitrosoglutathione,
pubmed-meshheading:12193733-Superoxides,
pubmed-meshheading:12193733-Transcription Factors,
pubmed-meshheading:12193733-U937 Cells
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| pubmed:year |
2002
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| pubmed:articleTitle |
Activation of peroxisome proliferator-activated receptor gamma by nitric oxide in monocytes/macrophages down-regulates p47phox and attenuates the respiratory burst.
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| pubmed:affiliation |
Institute of Cell Biology, University of Kaiserslautern, Germany.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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