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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
36
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pubmed:dateCreated |
2000-10-13
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pubmed:abstractText |
The efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) is considered to be a result of their inhibitory effect on cyclooxygenase (COX) activity. Here, we report that flufenamic acid shows two opposing effects on COX-2 expression; it induces COX-2 expression in the colon cancer cell line (HT-29) and macrophage cell line (RAW 264.7); conversely, it inhibits tumor necrosis factor alpha (TNFalpha)- or lipopolysaccharide (LPS)-induced COX-2 expression. This inhibition correlates with the suppression of TNFalpha- or LPS-induced NFkappaB activation by flufenamic acid. The inhibitor of extracellular signal-regulated protein kinase, p38, or NFkappaB does not affect the NSAID-induced COX-2 expression. These results suggest that the NSAID-induced COX-2 expression is not mediated through activation of NFkappaB and mitogen-activated protein kinases. An activator of peroxisome proliferator-activated receptor gamma, 15-deoxy-Delta(12,14)-prostaglandin J(2), also induces COX-2 expression and inhibits TNFalpha-induced NFkappaB activation and COX-2 expression. Flufenamic acid and 15-deoxy-Delta(12,14)-prostaglandin J(2) also inhibit LPS-induced expression of inducible form of nitric-oxide synthase and interleukin-1alpha in RAW 264.7 cells. Together, these results indicate that the NSAIDs inhibit mitogen-induced COX-2 expression while they induce COX-2 expression. Furthermore, the results suggest that the anti-inflammatory effects of flufenamic acid and some other NSAIDs are due to their inhibitory action on the mitogen-induced expression of COX-2 and downstream markers of inflammation in addition to their inhibitory effect on COX enzyme activity.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/15-deoxy-delta(12,14)-prostaglandin...,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Flufenamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NOS2 protein, human,
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/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin D2,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Sulindac,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/sulindac sulfide
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
275
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
28173-9
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pubmed:dateRevised |
2011-10-27
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pubmed:meshHeading |
pubmed-meshheading:10866999-Adenocarcinoma,
pubmed-meshheading:10866999-Animals,
pubmed-meshheading:10866999-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:10866999-Colonic Neoplasms,
pubmed-meshheading:10866999-Cyclooxygenase 2,
pubmed-meshheading:10866999-Enzyme Induction,
pubmed-meshheading:10866999-Flufenamic Acid,
pubmed-meshheading:10866999-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:10866999-Humans,
pubmed-meshheading:10866999-Isoenzymes,
pubmed-meshheading:10866999-Lipopolysaccharides,
pubmed-meshheading:10866999-Macrophages,
pubmed-meshheading:10866999-Membrane Proteins,
pubmed-meshheading:10866999-Nitric Oxide Synthase,
pubmed-meshheading:10866999-Nitric Oxide Synthase Type II,
pubmed-meshheading:10866999-Prostaglandin D2,
pubmed-meshheading:10866999-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:10866999-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:10866999-Sulindac,
pubmed-meshheading:10866999-Transcription Factors,
pubmed-meshheading:10866999-Tumor Cells, Cultured,
pubmed-meshheading:10866999-Tumor Necrosis Factor-alpha
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pubmed:year |
2000
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pubmed:articleTitle |
Two opposing effects of non-steroidal anti-inflammatory drugs on the expression of the inducible cyclooxygenase. Mediation through different signaling pathways.
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pubmed:affiliation |
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 70808, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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