Source:http://linkedlifedata.com/resource/pubmed/id/15178710
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2004-6-30
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| pubmed:abstractText |
Nitric oxide (NO(.-)) contributes to vascular collapse in septic shock and regulates inflammation. Here, we demonstrate in lipopolysaccharide (LPS)-stimulated human THP-1 cells and monocytes that NO(.-) regulates interleukin (IL)-8 and tumor necrosis factor alpha (TNF-alpha) by distinct mechanisms. Dibutyryl-cyclic guanosine 5'-monophosphate (cGMP) failed to simulate NO(.-)-induced increases in TNF-alpha or IL-8 production. In contrast, dibutyryl-cyclic adenosine monophosphate blocked NO(.-)-induced production of TNF-alpha (P=0.009) but not IL-8. NO(.-) increased IL-8 (5.7-fold at 4 h; P=0.04) and TNF-alpha mRNA levels (2.2-fold at 4 h; P=0.037). However, nuclear run-on assays demonstrated that IL-8 transcription was slightly decreased by NO(.-) (P=0.08), and TNF-alpha was increased (P=0.012). Likewise, NO(.-) had no effect on IL-8 promoter activity (P=0.84) as measured by reporter gene assay. In THP-1 cells and human primary monocytes treated with actinomycin D, NO(.-) had no effect on TNF-alpha mRNA stability (P>0.3 for both cell types) but significantly stabilized IL-8 mRNA (P=0.001 for both cell types). Because of its role in mRNA stabilization, the p38 mitogen-activated protein kinase (MAPK) pathway was examined and found to be activated by NO(.-) in LPS-treated THP-1 cells and human monocytes. Further, SB202190, a p38 MAPK inhibitor, was shown to block NO(.-)-induced stabilization of IL-8 mRNA (P<0.02 for both cell types). Thus, NO(.-) regulates IL-8 but not TNF-alpha post-transcriptionally. IL-8 mRNA stabilization by NO(.-) is independent of cGMP and at least partially dependent on p38 MAPK activation.
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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 AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
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,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
0741-5400
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
76
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
278-87
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:15178710-Blotting, Western,
pubmed-meshheading:15178710-Cell Line,
pubmed-meshheading:15178710-Cyclic AMP,
pubmed-meshheading:15178710-Cyclic GMP,
pubmed-meshheading:15178710-Enzyme Activation,
pubmed-meshheading:15178710-Enzyme Inhibitors,
pubmed-meshheading:15178710-Humans,
pubmed-meshheading:15178710-Interleukin-8,
pubmed-meshheading:15178710-Leukocytes, Mononuclear,
pubmed-meshheading:15178710-Lipopolysaccharides,
pubmed-meshheading:15178710-Mitogen-Activated Protein Kinases,
pubmed-meshheading:15178710-Nitric Oxide,
pubmed-meshheading:15178710-Protein Processing, Post-Translational,
pubmed-meshheading:15178710-RNA, Messenger,
pubmed-meshheading:15178710-RNA Stability,
pubmed-meshheading:15178710-Transfection,
pubmed-meshheading:15178710-Tumor Necrosis Factor-alpha,
pubmed-meshheading:15178710-Up-Regulation,
pubmed-meshheading:15178710-p38 Mitogen-Activated Protein Kinases
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| pubmed:year |
2004
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| pubmed:articleTitle |
Nitric oxide post-transcriptionally up-regulates LPS-induced IL-8 expression through p38 MAPK activation.
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| pubmed:affiliation |
Bldg. 10, Rm. 7D43, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
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| pubmed:publicationType |
Journal Article
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